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Physical Activity, Exercise, and Inflammatory Markers in Older Adults: Findings from The Health, Aging and Body Composition Study
Abstract
To examine the association between physical activity and inflammatory markers, with consideration for body fatness and antioxidant use.
Cross-sectional study, using baseline data from the Health, Aging and Body Composition Study.
Metropolitan areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee.
Black and white, well-functioning men and women (N=3,075), aged 70 to 79.
Interviewer-administered questionnaires of previous-week household, walking, exercise, and occupational/volunteer physical activities. Analysis of covariance was used to examine the association between activity level and serum C-reactive protein (CRP), interleukin-6 (IL-6), and plasma tumor necrosis factor alpha (TNFalpha) with covariate adjustment. Antioxidant supplement use (multivitamin, vitamins E or C, beta carotene) was evaluated as an effect modifier of the association.
Higher levels of exercise were associated with lower levels of CRP (P<.01), IL-6 (P<.001), and TNFalpha (P=.02) (e.g., CRP=1.95 mg/L for no exercise and 1.72 for >180 min/wk). Adjustment for body fatness attenuated the associations somewhat. Use of antioxidant supplements modified the CRP (P(interaction)=.01) and IL-6 (P(interaction)=.08) associations such that concentrations were low in those taking supplements (e.g., CRP=1.79-1.84 across exercise levels) and higher in nonsupplement users who did no exercise (2.03) than in those who did the most (1.72). Among nonexercisers, higher levels of other physical activity were related to lower levels of CRP (P<.01) and IL-6 (P=.02) but not TNFalpha (P=.36), even after accounting for body fat.
Inflammatory markers are lower in older adults with higher levels of exercise and nonexercise activity and in antioxidant supplement users regardless of exercise level.
... Relevant studies were further identified by screening (systematic) reviews and meta-analyses. Nine studies reporting changes in inflammatory markers in relation to OPA activity levels were identified (11,(14)(15)(16)(17)(18)(19)(20)(21) and included in the narrative analysis. ...
... Exercise, but also non-exercise PA, such as occupational or household work, has been reported to result in lower levels of circulating CRP, interleukin 6 (IL-6), and tumor necrosis factoralpha (TNF-α) in the elderly (15). Moderate weekly PA, regardless of leisure or occupational context, was found to correlate with the modulation of circulating inflammatory markers (16). ...
... Overall, due to the heterogeneity in the design of the few available studies (11,(14)(15)(16)(17)(18)(19)(20)(21), still very little is known about the association between OPA "intensity" and inflammatory markers, which are easily impacted by pre-existing comorbidities and immune-modulating medication, but also by (blood) sampling timepoints in relation to diurnal rhythm and hours since PA (54, 55). Proposed reasons for the frequently reported lack of health benefits of OPA in contrast to leisure-time PA are the suboptimal design of OPA for improving cardiorespiratory fitness, particularly in terms of (potentially harmful) working posture, intensity, or duration of working tasks; furthermore, uncontrolled elevation of 24 h heart rate and blood pressure (particularly by heavy lifting work), lack of sufficient recovery time between intensive tasks, and limited control over work-associated physical and psychosocial stressors (45) are potential proinflammatory hazards. ...
Background
Physical activity (PA) is beneficial for preventing several conditions associated with underlying chronic inflammation, e. g., cardiovascular disease (CVD) and cancer. While an active lifestyle appears to have anti-inflammatory effects, high levels of occupational PA (OPA) were associated with inflammation and elevated mortality risks. We aimed to summarize the current knowledge (1) on the association between inflammation and OPA and (2) its implications for health and mortality.
Methods and results
This mini-review summarized relevant literature published before January 2023 using established scientific databases and sources. For the primary outcome, observational studies (S) reporting immunological effects (O) in subjects (P), with high (I) vs. low OPA (C), were included. For secondary outcomes, i.e., morbidity and mortality associated with inflammatory processes, (systematic) reviews were included. While “active” occupations and “moderate” OPA appear to have beneficial effects, low (particularly sedentary) and “high-intensity” OPA (particularly including heavy lifting tasks) were associated with inflammation and (CVD and cancer-related) mortality; higher leisure-time PA has been almost consistently associated with lower proinflammatory markers and all-cause mortality risks. Workplace interventions appear to counter some of the observed health effects of unfavorable work strain.
Conclusion
The few studies addressing OPA “intensity” and inflammatory markers are largely heterogeneous regarding OPA classification and confounder control. Sedentary and “heavy” OPA appear to promote proinflammatory effects. In addition to targeted management of work-related physical strain and hazardous environmental co-factors, occupational health providers should focus on employer-initiated exercise interventions and the promotion of leisure-time PA.
... As per the results of the present study, eight weeks of resistance training had no significant effect on IL-6 and TNF-α in non-athlete women (pre-and post-test), and in this regard, there was no significant difference between the two types of resistance training with and without vascular occlusion. Previous studies have shown that aerobic exercise reduces plasma levels of TNF-α (Pitsavos et al., 2005), and IL-6 (Colbert et al., 2004). In contrast, other studies have shown that physical activity changes the serum levels of TNF-α (Bruunsgaard et al., 2004) and IL-6 (Bruunsgaard et al., 2004). ...
... This hypothesis has been proven in previous studies (Haghighi et al., 2005), but this is not observed in the present study, which may be due to the health of the present subjects. It seems that obesity (due to the production and gene expression of cytokines associated with inflammation of TNF-α and IL-6) is a risk factor that is strongly associated with high levels of inflammation (Colbert et al., 2004), thus reducing body fat and increased lipolysis due to physical activity is a mechanism that reduces inflammation. As mentioned, in the present study the subjects were healthy non-athlete girls of normal weight. ...
... Therefore, it seems reasonable not to see inflammatory cytokine change in this study. However, a number of epidemiological studies have suggested that the relationship between more physical activity and higher physical fitness with less inflammation is independent of total obesity and abdominal obesity (Colbert et al., 2004). ...
Resistance training is associated with reduced risk of low-grade inflammation related diseases. This study aimed to consider the effect of two methods of resistance training with and without vascular occlusion on changes in some serum cytokines in young non-athlete women. Thirty non-athlete women (20 to 30 years of age) were randomly divided into three groups (n=10 in each): resistance training without vascular occlusion (traditional), resistance training with vascular occlusion, and a control group. Resistance training was conducted three sessions for 8 weeks. In the vascular occlusion group, prior to the main exercise, the proximal part of both thighs was closed with a rubber tourniquet and the resistance exercise was performed with an intensity of 20-30% 1-repetition maximum (1RM) until fatigue. In the group without vascular occlusion, the same exercise were performed with similar intensity (with 70-80% 1RM until fatigue). Serum interleukin (IL)-15, IL-6, and tumour necrosis factor-alpha (TNF-α) were measured by ELISA method. One-way ANOVA was employed to compare the changes in the studied variables. The results show that serum levels of IL-6 and TNF-α and IL-15 do not have a significant change in groups with and without obstruction (P>0.05). Numerous studies have evaluated the positive effects of vascular occlusion on muscle hypertrophy and strength during rehabilitation. According to the results of the present study, it seems that the use of vascular occlusion exercise has less effect on inflammatory or IL-15.
... IL-6 holds a dominant role in the acute phase of inflammatory response, participates in the development of atherosclerosis, and constitutes a strong prognostic mortality marker along with hs-CRP and fibrinogen [9,10]. High sensitivity CRP, a nonspecific inflammatory marker found in dysfunctional vascular endothelium and early atheromatous lesions, is proven to be an independent prognostic marker of cardiovascular disease in the general adult population [9,11]. ...
... This finding shows the beneficial effect of physical activity on muscle mass and IL-6 levels during adolescence, eventually reducing cardiovascular risk. Moreover, lower levels of IL-6 have been associated in literature with increased physical activity in adults [11,30,31]. ...
... In previous studies on the general population, increased physical activity was associated with a lower CRP level (19-35%) than those with a sedentary life style [9,11]. Instead, in our study on T1D children and adolescents, physical activity was not related to hs-CRP, most likely due to the chronic inflammatory state caused by diabetes. ...
Adipokines are a superfamily of cell signaling proteins produced by the adipose tissue. This study’s purpose was to reveal the association of adipokines (leptin, adiponectin), hs-CRP, and IL-6 with well-known cardiovascular risk factors (lipid profile, diabetes control, obesity, physical activity) in children and adolescents with T1D. This cross-sectional study included 80 participants (36 boys) with T1D, aged (mean ± SD) 14.8 ± 3.4 years. Body Mass Index (BMI), metabolic profile, and level of physical activity were assessed (using pedometers) for evaluation of their effect on serum leptin, adiponectin, IL-6, and hs-CRP. Leptin levels were associated with BMI (beta = 0.184, p < 0.001), waist to hip ratio (beta = −2.017, p = 0.022), Low Density Lipoprotein-C (LDL-C) (beta = 0.021, p = 0.005), and fat mass (beta = 14.07, p < 0.001). Adiponectin was correlated with waist to height ratio (beta = 0.048, p = 0.006), ΒΜΙ (beta = −0.056, p = 0.005), and muscle mass (beta = −0.013, p = 0.020). Interestingly, hs-CRP was associated with weight (beta = 0.035, p < 0.001), ΒΜI (beta = 0.186, p < 0.001), fat mass (beta = 5.2859, p = 0.004), and muscle mass (beta = 0.027, p = 0.008). Multiple regression analysis of muscle mass unveiled associations with log hs-CRP (beta = −1.237, p = 0.014) and inverse IL−6 (beta = 18.57, p = 0.01). Finally, multiple regression models of fat mass unveiled associations with physical activity (7-day-total-step-count) (beta = −3.90 × 10⁻⁷, p = 0.027), Inverse IL-6 (beta = −0.1572, p = 0.009), and squared leptin (beta = 0.0077, p = 0.03). This study reports a positive association of leptin with LDL-C, BMI, fat mass, and hip circumference and a negative association of adiponectin with BMI and muscle mass. Finally, hs-CRP was associated with HbA1c, fat mass, and BMI. We propose that leptin, adiponectin, and hs-CRP could be used as prognostic indicators of cardiovascular risk in children with T1D.
... With population aging, it is becoming increasingly critical to maintain physical health, particularly for preventing conditions such as sarcopenia, which is characterized by the progressive loss of muscle mass and function [1][2][3][4][5][6]. Exercise has long been recognized as a key factor in promoting healthy aging by improving muscle mass and reducing body fat [7][8][9][10][11][12]. Furthermore, exercise represents a non-pharmacological approach for preventing and improving metabolic diseases through various programs [13][14][15]. ...
... Based on a literature review [7,9,13,[34][35][36], approximately 60 participants were required from each site to demonstrate a program effect. Assuming a 20% attrition rate, we planned to enroll approximately 70 participants. ...
Objectives
With population aging, personalized exercise programs considering clinical and demographic factors like sex, age, and physical activity level are essential; however, research on their effects remains limited. We aimed to evaluate the effectiveness of a Global Physical Activity Questionnaire-based graded personalized exercise program tailored for middle-aged adults aged 40–69 years.
Participants
We enrolled 71 middle-aged adults in their 40s, 50s, and 60s (approximately 20 participants per age group) in a parallel-group randomized controlled trial.
Intervention
Participants were assigned using age-stratified randomization to a treatment or control group. Participants were categorized into three levels according to weekly physical activity measured by the Global Physical Activity Questionnaire and physical activity guidelines for adults. Each participant’s grade was determined by applying equal weight adjustments for sex, age, and physical activity level, and the participants were assigned an exercise program corresponding to their grade. The exercise intervention consisted of a circuit training program alternating between aerobic and anaerobic exercises. The control group was instructed to maintain their usual physical activity levels.
Main outcome measures
Changes from before to after exercise in clinical results (body composition, physical fitness, ultrasound-measured muscle/fat thickness, and biochemical data) were recorded during the 8-week exercise program and differences between pre- and post-exercise values of the groups were analyzed using the t-test and Wilcoxon rank-sum test.
Results
Among 64 participants who had completed the program, 33 (51.5%) participated in the exercise program. The exercise program significantly increased abdominal muscle thickness (p < 0.01), reduced body fat percentage (p = 0.02) and waist circumference (p = 0.01), and positively affected various physical fitness indicators.
Conclusions
This study demonstrated the beneficial effects of a graded personalized exercise program on muscle thickness, body fat, and physical fitness and offers key data to support early preventive exercise programs in middle-aged adults to mitigate the risk of sarcopenia in later life.
Trial registration
Registered on November, 29, 2024 at cris.nih.go.kr identifier KCT0009970.
... Several large studies on population-based cohorts have investigated the effects of exercise on chronic inflammation, including the British Regional Heart Study [73], the Third National Health and Nutrition Examination Survey (NHANES III) [74,75], the Cardiovascular Health Study [76], the Men's Health Professionals Follow-up Study, the Nurses' Health Study II [77], the MacArthur Studies of Aging [78], the Multi-Ethnic Study of Atherosclerosis (MESA) [79], the CHIANTI study [80], and the Health, Aging, and Body Composition Study (Health ABC) [81]. These studies provide data suggesting an inverse association between CRP concentration and physical activity [71]. ...
... Individuals running more than four hours per week had 4% lower soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2, 6% lower IL-6, and 49% lower CRP compared to those running less than half an hour per week. Additionally, in the ATTICA study, physically active individuals with metabolic syndrome demonstrated 30% lower IL-6, 15% lower TNFα, 19% lower serum amyloid-A (SAA), and 15% lower white blood cell (WBC) counts compared to sedentary individuals [71,77,78,[81][82][83]. These results strongly suggest that physical activity is associated with lower systemic inflammation, potentially reducing the risk of chronic disease and cancer. ...
Simple Summary
Racial healthcare disparities, driven by adverse living conditions, environmental factors, and systemic biases, significantly affect Black Americans, and they are associated with increased oxidative stress, inflammation, and, in turn, chronic diseases like cardiovascular disease and cancer. Addressing these disparities requires comprehensive systemic reforms alongside additional strategies such as increased exercise, stress reduction, and anti-inflammatory diets. This review highlights the relevant literature and aims to encourage further research on this important topic.
Abstract
The impact of racial healthcare disparities has been well documented. Adverse social determinants of health, such as poverty, inadequate housing, and limited access to healthcare, are intricately linked to these disparities and negative health outcomes, highlighting the profound impact that social and economic factors have on individuals’ overall well-being. Recent evidence underscores the role of residential location on individual health outcomes. Despite the importance of a healthy lifestyle, regular physical activity, balanced nutrition, and stress management for favorable health outcomes, individuals living in socioeconomically disadvantaged areas may face obstacles in achieving these practices. Adverse living conditions, environmental factors, and systemic biases against Black Americans perpetuate allostatic load. This, compounded by decreased physical activity and limited healthy food options, may contribute to increased oxidative stress and inflammation, fundamental drivers of morbidities such as cardiovascular disease and cancer. Herein, we perform a narrative review of associations between healthcare disparities, chronic stress, allostatic load, inflammation, and cancer in Black Americans, and we discuss potential mechanisms and solutions. Additional research is warranted in the very important area of cancer disparities.
... Moreover, CRP and IL-6 exhibit higher sensitivity compared to TNF-α. The lack of TNF-α elevation may also be associated with the duration of exercise, as most studies (Hammett et al., 2004;Kohut et al., 2006;Nicklas et al., 2008;Vieira et al., 2009) show a reduction in systemic inflammatory markers after at least 24 weeks of intervention, while shorter intervention durations (less than 24 weeks) have no significant impact on inflammatory markers [ (Colbert et al., 2004;Martins et al., 2010) ] . Furthermore, within the confines of this study, there is notable heterogeneity observed in the levels of CRP, TNF-α, and IL-6. ...
... Furthermore, the nuanced age-related variations in the sensitivity of the anti-inflammatory system may contribute to disparate responses to identical interventions. As individuals progress in age, there is a gradual attenuation of immune function, instigating the progression of inflammatory processes (Colbert et al., 2004). Even under ostensibly healthy conditions, older individuals manifest a 2-4fold elevation in pro-inflammatory cytokines and acute-phase proteins when compared to their younger counterparts (Bruunsgaard and Pedersen, 2003). ...
In the realm of obesity and overweight, the risk of chronic diseases significantly escalates, closely intertwined with inflammatory factors. Research suggests that specific exercise interventions, particularly aerobic exercise and resistance exercise, can have beneficial effects on inflammation levels. However, debates persist regarding the actual impact of exercise in the obese and overweight population. We employed meta-analysis research methods and searched the China National Knowledge Infrastructure Wanfang Data, PubMed, and Web of Science databases to gather controlled experiments on the effects of resistance exercise or aerobic exercise on C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Two researchers independently conducted literature screening and data extraction. The quality of the literature was assessed according to the Cochrane Handbook standards, and subgroup analyses of CRP, IL-6, and TNF-α were performed using RevMan 5.4 software. Through quantitative synthesis of results from 22 selected studies encompassing a total of 1,135 research subjects, this study systematically explored the specific regulatory effects of different exercise modalities on inflammatory markers in the obese and overweight population. The findings indicate that both aerobic exercise and resistance exercise effectively reduce CRP levels in obese individuals, with aerobic exercise demonstrating a more pronounced effect. Aerobic exercise also significantly lowers IL-6 levels, while the impact of resistance exercise on IL-6 is relatively minor. However, in terms of reducing TNF-α levels, neither modality appears to exert a significant effect. Overall, exercise, especially aerobic exercise, emerges as a positive regulator of inflammatory markers in the context of obesity and overweight.
... Accattato et al. (2017) reported that there was no change in TNF-α values after walking exercise on a treadmill for 20 min 3 days a week with 30 volunteers [93]. Colbert et al. (2004) reported that TNF-α (p < 0.2) decreased significantly after high levels of exercise [94]. In another study, Jiménez-Maldonado et al. ...
... Accattato et al. (2017) reported that there was no change in TNF-α values after walking exercise on a treadmill for 20 min 3 days a week with 30 volunteers [93]. Colbert et al. (2004) reported that TNF-α (p < 0.2) decreased significantly after high levels of exercise [94]. In another study, Jiménez-Maldonado et al. ...
Background and Objectives: This study aimed to investigate the impact of moderate-intensity physical exercise on serum inflammation markers and the immune system in rats that were fed a high-fat diet (HFD) with intermittent fasting. Materials and Methods: A total of 48 Wistar albino male rats were included in the study and divided into eight groups, each consisting of six rats. Group 1 served as the control group (CG), receiving a standard diet. Group 2 followed the standard nutrition program with intermittent fasting (CG + IF). Group 3 underwent exercise with a standard diet (CG + E). Group 4 underwent both a standard diet with intermittent fasting and exercise (CG + IF + E). Group 5 was fed a high-fat diet (HFD). Group 6 received a high-fat diet with intermittent fasting (HFD + IF). Group 7 followed a high-fat diet with exercise (HFD + E). Group 8 underwent both a high-fat diet with intermittent fasting and exercise (HFD + IF + E). The study lasted for 8 weeks. Results: The results of the analysis show that lymphocyte cell levels in groups HFD + IF, HFD + IF, and HFD + IF + E were higher compared to groups CG-HFD (p < 0.05). Additionally, B lymphocyte and monocyte cell levels were higher in group HFD + IF + E compared to groups CG, CG + IF, and CG + IF + E, as well as CG, CG + IF, and CG + E, respectively. TNF-α levels were significantly higher in group HFD compared to the other groups. Furthermore, IL 10 levels were higher in group HFD + IF + E compared to the other groups. Conclusions: These findings indicate that moderate exercise and intermittent fasting, particularly in groups fed a high-fat diet, increased anti-inflammatory cytokine levels, and certain immune system cell counts, while decreasing pro-inflammatory cytokine levels.
... IL-6 is a pro-inflammatory cytokine produced mainly by fibroblasts and adipose tissue cells. Recent research findings indicate that physical activity is associated with lower levels of IL-6 [7][8][9]. ...
... Elevated levels of hs-CRP are related to atherosclerosis and strongly predict endothelial dysfunction, comprising for cardiologists one more modifiable risk factor for CVD management. According to extensive scientific literature, higher levels of physical activity are related to lower hs-CRP levels [8,10]. ...
Purpose
Individuals with Type-1-Diabetes (T1D) are at higher risk of having premature cardiovascular-disease (CVD). Physical activity and healthy lifestyle are major components in the prevention of diabetes’ related comorbidities and complications.
The aim of this study was to investigate the impact of physical activity, eating habits and quality of life in children and adolescents with T1D on diabetic control, cardiovascular and biochemical profile, infection indices, and adipokine levels.
Methods
This cross-sectional study involved 80 participants (36 boys/44 girls) with T1D, aged (mean ± SD) 14.9 ± 3.4 years, who attended the Diabetes and Metabolism Clinic of a University Children’s Hospital, using anthropometric studies, lipid profile, high-sensitivity-C-Reactive-Protein(hs-CRP), Interleukin-6(IL6), leptin and adiponectin levels. Physical activity was assessed with pedometers (total-steps/week) and questionnaire.
Results
In 20(25%) children the level of exercise was >75th percentile, in 20(25%) <25th percentile and in 40(50%) children ranged between 25–75th percentile, respectively. Higher levels of physical activity were associated with weight (beta = −0.053, p < 0.001), waist circumference (beta = −0.077, p < 0.001), BMI (beta = −0.167, p = 0.009), muscle mass (beta = −0.0619, p = 0.001) and HDL-C (beta = 0.039, p = 0.033). Quality of life was positively related to weight (beta = 5.49511, p = 0.002), waist circumference (beta = 6.593345, p = 0.012), muscle mass (beta = 7.324088, p < 0.001) and T1D duration (beta = 19.22442, p = 0.005). Lipid profile was positively associated with sweets and chocolate consumption (beta = 0.348, p < 0.05), while vegetable (beta = −0.245, p < 0.05) and white milk consumption (beta = −0.2295, p < 0.05) were negatively associated with waist/height ratio.
Conclusions
In the present study, higher levels of physical activity were associated with improved lipid profile (HDL-C, triglycerides) and body composition [waist circumference, Body-Mass-Index (BMI] of children and adolescents with T1D. Higher scoring in quality-of-life questionnaires were related to older children with longer diabetes duration. Unhealthy eating habits unfavorably affected lipid profile and body composition in T1D youth.
... First Release September 15 2022 hypothesis is supported by several studies in the general population that demonstrated a clear association between higher levels of physical activity, reductions in proinflammatory cytokine signaling, and lower systemic inflammation. [7][8][9][10] Though studies in the general population have observed favorable effects of exercise on immune function, how physical activity influences systemic inflammation in the context of immune-mediated inflammatory diseases such as RA remains poorly understood and represents an important question in need of further investigation. ...
... Studies in the general population have found that higher levels of physical activity associate with lower inflammatory biomarkers, including C-reactive protein and tumor necrosis factor (TNF)-α, even after adjusting for excess adiposity. [7][8][9][10] Our results are consistent with these observations, as we observed an association between physical activity and attenuation of several proinflammatory signaling pathways implicated in RA pathogenesis, including CD40, STAT3, TREM-1, IL-17A, IL-8, TLR, and type I IFN. 19 Further, our gene expression data demonstrated lower TNF activation among the most active relative to the least active patients in this RA cohort. ...
Objective:
While general population studies have shown inverse associations between physical activity and common inflammatory biomarkers, the effects of physical activity on inflammatory gene expression and signaling pathways in rheumatoid arthritis (RA) remain unknown. We aimed to determine whether physical activity independently associates with expression of inflammatory genes among people with RA.
Methods:
This was a prospective observational study of adults with RA. Physical activity was measured by quantitative actigraphy over 7 consecutive days, and peripheral blood collected during the same time period was used for RNA sequencing followed by differential gene expression, pathway, and network analyses.
Results:
Actigraphy and RNA sequencing data was evaluated on 35 patients. The cohort mean age was 56±12 years, 91% female, 31% white, 9% African American, 9% Asian, 40% Hispanic. We found 767 genes differentially expressed (padj<0.1) between patients in the greatest versus lowest physical activity tertiles, after adjusting for sex, age, race, and ethnicity. The most active patients exhibited dose-dependent downregulation of several immune signaling pathways implicated in RA pathogenesis. These included CD40, STAT3, TREM-1, IL-17a, IL-8, toll-like receptor and interferon signaling pathways. Upstream cytokine activation state analysis predicted reduced activation of TNF-alpha and interferon in the most active group. In sensitivity analyses we adjusted for RA disease activity and physical function and found consistent results.
Conclusion:
RA patients who were more physically active had lower expression of immune signaling pathways implicated in RA pathogenesis, even after adjusting for disease activity, suggesting that physical activity may confer a protective effect in RA.
... Sarcopenia, which is a hallmark of ageing and a measure of frailty, has been associated with chronic exposure to oxidative stress, inflammation and reduction in antioxidant capacity [32][33][34]. Raised levels of IL-6, which is independent of body composition, have been associated with reduced physical activity and increasing frailty [35,36]. These findings may form part of the notion that fitter individuals have a lower baseline inflammatory state, which renders them to be more resilient and better able to adapt to stresses intraoperatively through mitochondrial protective mechanisms. ...
More complex surgeries are being performed in increasingly sicker patients, resulting in a greater burden of postoperative morbidity. Delineating the metabolic and bioenergetic changes that occur in response to surgical stress may further our understanding about how humans respond to injury and aid the identification of resilient and frail phenotypes. Skeletal muscle biopsies were taken from patients undergoing hepato-pancreatico-biliary surgery at the beginning and end of the procedure to measure mitochondrial respiration and thiol status. Blood samples were taken at the same timepoints to measure markers of inflammation and systemic redox state. A sub-group of patients underwent cardiopulmonary exercise testing prior to surgery, and were assigned to two groups according to their oxygen consumption at anaerobic threshold (≤10 and >10 mL/kg/min) to determine whether redox phenotype was related to cardiorespiratory fitness. No change in mitochondrial oxidative phosphorylation capacity was detected. However, a 26.7% increase in LEAK (uncoupled) respiration was seen after surgery (P = 0.03). Free skeletal muscle cysteine also increased 27.0% (P = 0.003), while S-glutathionylation and other sulfur and nitrogen-based metabolite concentrations remained unchanged. The increase in LEAK was 200% greater in fit patients (P = 0.004). Baseline plasma inflammatory markers, including TNF-⍺ and IL-6 were greater in unfit patients, 96.6% (P = 0.04) and 111.0% (P = 0.02) respectively, with a 58.7% lower skeletal muscle nitrite compared to fit patients. These data suggest that oxidative phosphorylation is preserved during the acute intraoperative period. Increase in free cysteine may demonstrate the muscle’s response to surgical stress to maintain redox balance. The differences in tissue metabolism between fitness groups suggests underlying metabolic phenotypes of frail and resilient patients. For example, increased LEAK in fitter patients may indicate mitochondrial adaptation to stress. Higher baseline measurements of inflammation and lower tissue nitrite in unfit patients, may reflect a state of frailty and susceptibility to postoperative demise.
... 58,59 Observational studies indicate that regular physical activity in the elderly correlates with high IL-10 and adiponectin levels, which are protective against AMD. [60][61][62][63][64][65][66] Moreover, MR analyses indicate that high circulating C-reactive protein (CRP) levels may increase the risk of AMD. 67,68 A meta-analysis of seven studies involving 275 participants demonstrated that exercise interventions effectively lowered CRP levels in hospitalized elderly individuals. ...
Objective
To investigate the causal effects of physical activity and sedentary traits on risk of Age-related macular degeneration (AMD).
Methods
A two-sample Mendelian randomization (MR) analysis was used to investigate the causal relationship between physical activity and risk of AMD. We used genome-wide association studies (GWAS) summary statistics from two publicly available biobank-scale cohorts: UK Biobank and FinnGen. Physical activity data were self-reported by 703,901 UK Biobank participants and sedentary behaviour data were gathered from 159,606 FinnGen participants. Our analysis primarily used the inverse variance weighted (IVW) method.
Result
Engaging in moderate-to-vigorous physical activity significantly reduced the risk of AMD with an odds ratio of 0.77 (95% CI: 0.66–0.89). However, leisure screen time showed a slight but non-statistically significant upward trend. Sedentary behaviour at work, sedentary commuting showed no causal effects on AMD risk.
Conclusions
This study used MR analysis to examine the causal relationship between physical activity, sedentary behaviour, and AMD. It offers genetic evidence suggesting that physical activity may protect against AMD, emphasizing the significance of lifestyle factors in maintaining ocular health.
... [54,[60][61][62] For instance, age and gender differences are main factors that play an important role in this relationship. [56,63,64] However, many experiments clearly illustrated that increasing age above 50 years is associated with elevated fat mass, decreased fat-free mass, and decreased PA. In young adults, long-term PA lowers fat mass and increases fat-free mass. ...
Introduction: Physical activity simply is any movement of the body that sustains and empowers physical fitness and overall health and wellness. Physical inactivity became a concern in the Kingdom of Saudi Arabia especially in females during the last few decades. The purpose of this study was to assess the physical activity patterns among female college students. Methods: A cross-sectional study was conducted among 658 female college students at Taibah University. The short form of the Arabic version of the International Physical Activity Questionnaire (IPAQ) was used to assess physical activity pattern. Additional data were collected on body mass index (BMI), body composition, including body fat percentage (BF%), visceral fat level (VFL), and skeletal muscle percent (SM%). Results: Overall, 37.5% of the students performed vigorous-intensity, and 44.9% performed moderate-intensity physical activity. Both BMI and BF% were significantly inversely associated with vigorous and moderate physical activity. These associations appeared to be stronger among students who performed vigorous physical activity for ≥75 min/week for BMI (aOR = 0.559, 95% CI 0.318-0.687) and BF% (aOR = 0.389, 95% CI 0.044-0.507) and moderate physical activity for ≥ 150 min/week for BMI (aOR = 0.580, 95% CI 0.205-0.812) and BF% (aOR = 0.320, 95% CI 0.124-0.402). Conclusion: Although both vigorous and moderate physical activity appeared to affect BMI and BF%, among college students who performed physical activity, our findings suggest the need for strategies to increase awareness among female students to be physically active to promote healthy lifestyles and substantial health benefits.
... Demographic factors included age (years), sex (men/women), race (White/Black), study site (Memphis/Pittsburgh), and education (high school graduate: yes/no). Health behaviors included smoking status (yes, no, and former smoker), alcohol use (>1 drink/day: yes/no), and interview-administered physical activity assessment (kcal/kg/ week) (15). Health status factors included a total number of prescription medications, body mass index (kg/m 2 ), sensory detection (monofilament insensitivity: none, 1.4 g, and 10 g), kidney function (Cystatin C > 1.0: yes/no), subclinical peripheral arterial disease (ankle arm index: ≤0.9, 0.9-1.3, ...
Background and Objectives
Fall injuries are prevalent in older adults, yet whether higher spending occurs after nonfracture (NFFI) and fracture is unknown. We examined whether incident fall injuries, including NFFI and fractures, were associated with higher Medicare spending in 12 months after incident events in older adults.
Research Design and Methods
The Health, Aging, and Body Composition Study included 1 595 community-dwelling adults (53% women, 37% Black; 76.7 ± 2.9 years) with linked Medicare Fee-For-Service (FFS) claims at 2000/01 exam. Incident outpatient and inpatient fall injuries (N = 448) from 2000/01 exam to December 31, 2008 were identified using the first claim with a nonfracture injury diagnosis code with a fall E-code, or a fracture diagnosis code with/without an E-code. Up to 3 participants without fall injuries (N = 1 147) were matched on nonfall events to 448 participants in the fall injury month. We calculated the change in monthly FFS spending in 12 months before versus after index events in both groups. Generalized linear regression with centered outcomes and gamma distributions examined the association of prepost expenditure changes with fall injuries (including NFFI and fractures) adjusting for related covariates.
Results
Monthly spending increased after versus before fall injuries (USD981), nonfracture (N = 105; USD1 277), and fracture (N = 343; USD890) injuries (all p < .0001). However, after adjusting for covariates in final models, fall injuries were not significantly associated with larger increases in spending/month versus nonfall events (differential increase: USD44.95 to 471.93 [95% CI: −USD965.02]).
Discussion and Implications
Although substantial increases occurred after injuries, with fracture and NFFI increasing similarly, changes in monthly spending after fall injury were not different compared to nonfall events. Our results contribute to the understanding of subsequent spending after fall injury that may inform further research on fall injury-related health care spending.
... positive impacts on the human body, one of which is its astonishing capacity to combat inflammation. Numerous scientific studies have repeatedly shown that physical activity can significantly lower inflammation levels 12,13 . Physical inactivity corresponds to a higher degree of inflammation, while engaging in physical activity has been shown to alleviate inflammation 14,15 . ...
Introduction: The intriguing link between periodontal disease severity and physical activity remains largely understudied, particularly in the Saudi Arabian population. Thus, the current research was intended to ascertain the effect of physical activity on the prevalence and indicators of periodontal diseases. Materials: The cross-sectional approach with convenience sampling was applied to the recruitment of 160 adult subjects attending gymnasiums, sports clubs, malls, primary health centres, and community dental health programs. Based on IPAQ scores, the participants were split into two distinct groups: a physically active group and a physically inactive group. The two study groups were compared with one another in terms of recorded parameters. The gathered data subsequently underwent statistical processing using SPSS 20.0. Results: Of the 160 subjects, 66.87% (n = 107) had gingivitis and 33.12% (n = 53) periodontitis. A lower mean PI (1.62±0.31) was observed in the physically active group compared to the physically inactive group (6.91±1.12). The physically active group had a mean BI of 19.01±4.53 and the inactive group 69.98±9.29. For physically active and inactive groups, mean PD measurements were 2.49±0.33 mm and 4.61±0.07 mm, respectively.Physically active individuals had a significantly lower mean CAL (2.98±0.88 mm) compared to the inactive group (5.37±1.02 mm). Parametric variances between groups are statistically significant (p<0.001). Conclusion: Insufficient engagement in physical activity has undeniably been identified as a risk factor for the development and severity of periodontal disease, marked by escalated indicators of gingivitis and periodontitis. The study findings unequivocally endorse the adoption of a consistent physical activity regimen as strategic initiatives to proactively address the incidence of inflammatory periodontal diseases. Many patients with different psychophysical characteristics seek periodontal therapy at dental clinics. This study alerts clinicians to the impact of physical inactivity in a wide-spectrum population and helps identify periodontal risk in sedentary patients. It also aids in treatment planning for these periodontally risky, physically inactive people. Bangladesh Journal of Medical Science Vol.23 (Special Issue) 2024 p.S20-S25
... www.nature.com/scientificreports/ hsCRP is influenced by numerous factors such as lack of physical activity, poor diet, smoking and elevated body-mass-index (BMI) [10][11][12][13] . These factors have been termed lifestyle-related risk factors (LRF). ...
The inflammatory burden as measured by high-sensitivity C-reactive Protein (hsCRP) is recognized as a cardiovascular risk factor, which can however be affected by lifestyle-related risk factors (LRF). Up-to-date the interplay between hsCRP, LRF and presence and extent of atherosclerotic disease is still largely unknown, which we therefore sought to investigate in a contemporary population-based cohort. We included participants from the cross-sectional population-based Hamburg City Health Study. Affected vascular beds were defined as coronary, peripheral, and cerebrovascular arteries. LRF considered were lack of physical activity, overweight, active smoking and poor adherence to a Mediterranean diet. We computed multivariable analyses with hsCRP as the dependent variable and LRF as covariates according to the number of vascular beds affected. In the 6765 individuals available for analysis, we found a stepwise increase of hsCRP concentration both according to the number of LRF present as well as the number of vascular beds affected. Adjusted regression analyses showed an independent association between increasing numbers of LRF with hsCRP levels across the extent of atherosclerosis. We demonstrate increasing hsCRP concentrations according to both the number of LRF as well as the extent of atherosclerosis, emphasizing the necessity of lifestyle-related risk factor optimization.
... While the change in lung function did not reach 7 the clinically significant levels that are published [29], the small changes observed at 8 population level can lead to overall shift of the average having substantial effects. 9 A potential mechanism for the accelerated lung function decline observed with low PA 10 is the long-term anti-inflammatory effects observed with PA [30,31]. Changes in fat 11 distribution associated with high levels of PA have been hypothesized to explain the 12 reduced rate of lung function decline [18,30]. ...
... В основе развития атеросклероза и "патологического старения" организма, по данным ряда исследований, лежит хроническое воспаление [22,23]. ФА умеренной интенсивности играет ключевую роль в предотвращении развития и прогрессирования и ИБС, и ССА, о чем свидетельствуют снижение уровня маркеров системного воспаления и коррекция эндотелиальной дисфункции [24]. Таким образом, при умеренном уровне ФА значимо повышается ожидаемая продолжительность жизни и качество жизни пациентов с ИБС и старческой астенией [25]. ...
... The details of the study population have been previously published. 22 We included 2121 of the 3075 participants, after applying the exclusions described, whose characteristics are shown in Table S1. Of the 954 excluded participants, 190 died during the first 3 years of the study. ...
Background:
This study aimed to determine if greater variability in body mass index (BMI) is associated with declines in physical functioning and incident disability in older adults.
Methods:
Included were participants from the Health, Aging and Body Composition Study who had semi-annual BMI data during the first 3 years of follow-up. Participants were categorized into quintiles of BMI variability, using two methods. The first method used average successive variability, whereas the second method adjusted these values to remove the variability due to net change in BMI over the 3-year period. Linear regression was used to assess the relationship between the two measures of BMI variability and net changes in BMI, fat mass index, appendicular lean mass index, and Health, Aging and Body Composition Physical Performance Score during the first 3 years of the study. Cox proportional hazard models were used to assess the relationship of BMI variability with the subsequent incidence of new disability, adjusting for confounding factors.
Results:
Among 2121 participants, those in the highest BMI variability quintile were more likely to lose both body mass (β: -0.086 [95% confidence interval, CI: -0.133, -0.040], P < 0.01) and fat mass (β: -0.059 [95% CI: -0.117, -0.002], P = 0.04) and had greater declines in physical performance score (β: -0.094 [95% CI: -0.162, -0.026], P < 0.01) compared to participants with the least variability in BMI. Participants with high BMI variability also had higher rates of incident disability (hazard ratio: 1.36 [95% CI: 1.07, 1.72], P = 0.01), independent of net BMI change.
Conclusions:
BMI variability in older adults is associated with decline in physical performance and incident disability. This relationship cannot be explained by net weight loss alone, supporting it as an independent feature of frailty.
... We included both physical activities performed in leisure time (for example, walking and running) and fitness club activities (for example, running on a treadmill, aerobics, or resistance training). It is this level of physical activity that is considered protective against the development of cardiovascular diseases by most authors [66][67][68]. According to the WHO criteria, overweight is defined as patients with a body mass index of 25 or over [69]. ...
The SERBP1 gene is a well-known regulator of SERPINE1 mRNA stability and progesterone signaling. However, the chaperone-like properties of SERBP1 have recently been discovered. The present pilot study investigated whether SERBP1 SNPs are associated with the risk and clinical manifestations of ischemic stroke (IS). DNA samples from 2060 unrelated Russian subjects (869 IS patients and 1191 healthy controls) were genotyped for 5 common SNPs—rs4655707, rs1058074, rs12561767, rs12566098, and rs6702742 SERBP1—using probe-based PCR. The association of SNP rs12566098 with an increased risk of IS (risk allele C; p = 0.001) was observed regardless of gender or physical activity level and was modified by smoking, fruit and vegetable intake, and body mass index. SNP rs1058074 (risk allele C) was associated with an increased risk of IS exclusively in women (p = 0.02), non-smokers (p = 0.003), patients with low physical activity (p = 0.04), patients with low fruit and vegetable consumption (p = 0.04), and BMI ≥25 (p = 0.007). SNPs rs1058074 (p = 0.04), rs12561767 (p = 0.01), rs12566098 (p = 0.02), rs6702742 (p = 0.036), and rs4655707 (p = 0.04) were associated with shortening of activated partial thromboplastin time. Thus, SERBP1 SNPs represent novel genetic markers of IS. Further studies are required to confirm the relationship between SERBP1 polymorphism and IS risk.
... Liu et al. outlined that rehabilitation may cause respiratory muscle strengthening and improvement of respiratory system function [11]. Physical activity can improve health in low-grade inflammation (associated with ageing) and COVID-19 [12][13][14][15][16]. The WHO highlighted that home-based physical activity provides a safe, cheap and controllable intervention for all ages affected by COVID-19 [17]. ...
Background
The clinical manifestation of COVID-19 is associated with infection and inflammation of the lungs, but there is evidence to suggest that COVID-19 may also affect the structure and function of the cardiovascular system. At present, it is not fully understood to what extent COVID-19 impacts cardiovascular function in the short- and long-term following infection. The aim of the present study is twofold: (i) to define the effect of COVID-19 on cardiovascular function (i.e. arterial stiffness, cardiac systolic and diastolic function) in otherwise healthy individuals and (ii) to evaluate the effect of a home-based physical activity intervention on cardiovascular function in people with a history of COVID-19.
Methods
This prospective, single-centre, observational study will recruit 120 COVID-19-vaccinated adult participants aged between 50 and 85 years, i.e. 80 with a history of COVID-19 and 40 healthy controls without a history of COVID-19. All participants will undergo baseline assessments including 12-lead electrocardiography, heart rate variability, arterial stiffness, rest and stress echocardiography with speckle tracking imaging, spirometry, maximal cardiopulmonary exercise testing, 7-day physical activity and sleep measures and quality of life questionnaires. Blood samples will be collected to assess the microRNA expression profiles, cardiac and inflammatory biomarkers, i.e. cardiac troponin T; N-terminal pro B-type natriuretic peptide; tumour necrosis factor alpha; interleukins 1, 6 and 10; C-reactive protein; d-dimer; and vascular endothelial growth factors. Following baseline assessments, COVID-19 participants will be randomised 1:1 into a 12-week home-based physical activity intervention aiming to increase their daily number of steps by 2000 from baseline. The primary outcome is change in left ventricular global longitudinal strain. Secondary outcomes are arterial stiffness, systolic and diastolic function of the heart, functional capacity, lung function, sleep measures, quality of life and well-being (depression, anxiety, stress and sleep efficiency).
Discussion
The study will provide insights into the cardiovascular implications of COVID-19 and their malleability with a home-based physical activity intervention.
Trial registration
ClinicalTrials.gov NCT05492552. Registered on 7 April 2022.
... Some epidemiological studies also support it. They demonstrate that even with acute activity, the baseline value of IL-6 levels rises (Cesari et al. 2004;Colbert et al. 2004;Panagiotakos et al. 2005). ...
DIABETES MELLITUS AND CYTOKINES
... Some epidemiological studies also support it. They demonstrate that even with acute activity, the baseline value of IL-6 levels rises (Cesari et al. 2004;Colbert et al. 2004;Panagiotakos et al. 2005). ...
... Interleukin-6 (IL-6), detected in 1986 as a B-cell differentiation factor, today is known as a multi-functional cytokine associated with immune and acute phase responses and plays a significant role in the pathogenesis of some autoimmune diseases [30]. Overproduction of IL-6 implicates a variety of chronic inflammatory diseases such as obesity, type 2 diabetes, atherosclerosis, and menopause [31,32] which are reduced by exercise in these populations [33,34]. Therefore, among the therapeutic strategies introduced to alleviate inflammation in postmenopausal women, exercise seems to be an effective, safe, and accessible intervention [35][36][37][38]. ...
Introduction: Menopause is a noticeable period in women's life accompanied by some physiological and psychological changes leading to health conditions such as obesity, overweight, cardiovascular, and other inflammatory diseases.
... Several cross-sectional studies have reported an association between a sedentary lifestyle and increased systemic inflammation levels in older adults [154,155] and a decline in the anti-inflammatory cytokine IL-10 [64]. A meta-analysis of 11 aerobic exercise intervention studies with a total of 1,138 participants has revealed that decreased levels of CRP, IL-6, TNFα in old participants occur as early as 12 weeks post-exercise training [156]. ...
Life expectancy has been on the rise for the past few decades, but healthy life expectancy has not kept pace, leading to a global burden of age-associated disorders. Advancing age is accompanied by a chronic increase in basal systemic inflammation, termed inflammaging, contributing towards an increased risk of developing chronic diseases in old age. This article reviews the recent literature to formulate hypotheses regarding how age-associated inflammaging plays a crucial role in driving chronic diseases and ill health in older adults. Here, we discuss how non-pharmacological intervention strategies (diet, nutraceutical supplements, phytochemicals, physical activity, microbiome-based therapies) targeting inflammaging restore health in older adults. We also consider alternative existing pharmacological interventions (Caloric restriction mimetics, p38 mitogen-activated protein kinase inhibitors) and explore novel targets (senolytics) aimed at combating inflammaging and optimising the ageing process to increase healthy lifespan.
... Evidence in older adults indicates that higher levels of exercise and physical activity were associated with reduced levels of CRP, IL-6, and TNF-α [150], although the cross-sectional nature of the investigation does not permit identification of a true cause-andeffect of exercise. However, such findings are corroborated by Kohut and colleagues who reported significant reductions in CRP, IL-6, and TNF-α following 10 months of moderate to vigorous AEx training (progressing from 45-80% VȮ 2peak ) in older adults [151]. ...
Globally, depression is a leading cause of disability and has remained so for decades. Antidepressant medications have suboptimal outcomes and are too frequently associated with side effects, highlighting the need for alternative treatment options. Although primarily known for its robust physical health benefits, exercise is increasingly recognized for its mental health and antidepressant benefits. Empirical evidence indicates that exercise is effective in treating individuals with depression; however, the mechanisms by which exercise exerts anti-depressant effects are not fully understood. Acute bouts of exercise have been shown to transiently modulate circulating levels of serotonin and norepinephrine, brain-derived neurotrophic factor, and a variety of immuno-inflammatory mechanisms in clinical cohorts with depression. However, exercise training has not been demonstrated to consistently modulate such mechanisms, and evidence linking these putative mechanisms and reductions in depression is lacking. The complexity of the biological underpinnings of depression coupled with the intricate molecular cascade induced by exercise are significant obstacles in the attempt to disentangle exercise's effects on depression. Notwithstanding our limited understanding of these effects, clinical evidence uniformly argues for the use of exercise to treat depression. Regrettably, exercise remains underutilized despite being an accessible, low-cost alternative/adjunctive intervention that can simultaneously reduce depression and improve overall health. To address the gaps in our understanding of the clinical and molecular effects of exercise on depression, we propose a model that leverages systems biology and multidisciplinary team science with a large-scale public health investment. Until the science matches the scale of complexity and burden posed by depression, our ability to advance knowledge and treatment will continue to be plagued by fragmented, irreproducible mechanistic findings and no guidelines for standards of care.
... Both short and long-term clinical trials suggest that increasing physical activity results in improvements in global and domain-specific cognitive function (Ngandu et al., 2015;Vidoni et al., 2015;Pontifex et al., 2016). Increasing physical activity may exert its effects on cognition by provoking metabolic and structural brain changes such as increasing brain volume, decreasing neuroinflammation, improving cerebral glucose metabolism, and enhancing functional connectivity (Colbert et al., 2004;Colcombe et al., 2006;Voss et al., 2010;Dougherty et al., 2017). ...
Introduction
Regular physical activity lowers risk for cognitive decline and neurodegenerative disorders. Older African Americans (AAs) have been underrepresented in trials that increased physical activity to improve cognitive outcomes.
Methods
56 sedentary, older, cognitively healthy AAs (avg. 69.2 ± 3.4 yrs. old) were randomized in 1:1 ratio into either a 12-week successful aging group (SAG) or a 12-week physical activity group (PAG). Participants in SAG attended weekly 60-min educational sessions in which healthy aging topics were discussed. Participants in PAG attended supervised physical activity sessions twice per week at local YMCAs (90–120 min/week) and were prescribed 2–3 days per week of home-based activity. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) assessed cognitive function. ANCOVA models compared mean 12-week change in global cognition and subdomain scores between groups with secondary analyses for sex differences. Effect sizes for RBANS were calculated.
Results
The RBANS global cognition score (SAG Est. 5.6 ± 1.8, effect size = 0.37, p = 0.003) and several subdomain scores (one-sample T tests, all p < 0.05) increased significantly within the SAG. Scores for global cognition increased more in SAG than in PAG (Change Estimate, PAG minus SAG: –4.6 ± 2.5 points, effect size = 0.31) at a trend level ( p = 0.072). SAG females increased their global cognition score more than PAG females and more than males in either PAG or SAG (all p < 0.035).
Discussion
A 12-week physical activity intervention (PAG) did not improve cognitive functioning among older AAs but a comparator healthy aging education program did. Inadequate physical activity dosage or duration, SAG members acting on health-related information from educational sessions, and/or social stimulation within the SAG may have contributed to these results. Future studies should combine socially engaging activities with vigorous physical activity for cognitive enhancement among cognitively healthy older African Americans.
Clinical Trial Registration
www.ClinicalTrials.gov , identifier NCT03474302.
... Systemic inflammation plays a major role in CAD etiopathogenesis [17] and routine inflammatory biomarkers (complete blood count, C-reactive protein) have proven their role for both acute and long-term cardiovascular risk assessment [18][19][20]. Physical activity decreases systemic markers of inflammation, thrombosis and endothelial dysfunction, and has a key role in preventing CAD [21][22][23]. The platelet to lymphocyte ratio (PLR) is an integrated reflection of two important opposite inflammatory pathways that can be easily calculated from a complete blood count. ...
Background and Objectives: Functional capacity (FC) assessed via cardiopulmonary exercise testing (CPET) is a novel, independent prognostic marker for patients with coronary artery disease (CAD). Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are two readily available predictors of systemic inflammation and cardiovascular event risk, which could be used as cost-effective predictors of poor FC. The purpose of this study was to evaluate the utility of NLR and PLR in predicting poor FC in patients with CAD and recent elective percutaneous coronary intervention (PCI). Materials and Methods: Our cross-sectional retrospective analysis included 80 patients with stable CAD and recent elective PCI (mean age 55.51 ± 11.83 years, 71.3% male) who were referred to a cardiovascular rehabilitation center from January 2020 to June 2021. All patients underwent clinical examination, cardiopulmonary exercise testing on a cycle ergometer, transthoracic echocardiography and standard blood analysis. Results: Patients were classified according to percent predicted oxygen uptake (% VO2 max) in two groups—poor FC (≤70%, n = 35) and preserved FC (>70%, n = 45). There was no significant difference between groups regarding age, gender ratio, presence of associated comorbidities, left ventricular ejection fraction and NLR. PLR was higher in patients with poor FC (169.8 ± 59.3 vs. 137.4 ± 35.9, p = 0.003). A PLR cut-off point of 139 had 74% sensitivity and 60% specificity in predicting poor FC. After multivariate analysis, PLR remained a significant predictor of poor functional status. Conclusions: Although CPET is the gold standard test for assessing FC prior to cardiovascular rehabilitation, its availability remains limited. PLR, a cheap and simple test, could predict poor FC in patients with stable CAD and recent elective PCI and help prioritize referral for cardiovascular rehabilitation in high-risk patients.
Bone stress injuries are pervasive among endurance runners due to repetitive sport-specific mechanical loading and a higher prevalence of low energy availability (i.e., inadequate dietary energy intake relative to exercise energy expenditure). Chronic endurance exercise promotes bone formation, thus, runners typically have higher bone mineral density (BMD) than non-weightbearing athletes and sedentary individuals. However, runners may experience increased bone resorption for hours to days following an endurance exercise bout. If recovery is insufficient, uncoupled bone turnover can pose a significant risk to their bone health. While skeletal-immune system crosstalk has been studied, the interaction during and after exercise in athletes is an emerging area of research. Nutritional interventions have been investigated for their effects on bone metabolism surrounding exercise. However, limited research has examined dietary protein intake in endurance athletes, particularly concerning its effects on bone metabolism and osteoimmunology. This narrative review provides an overview of the evidence on the effects of endurance exercise and dietary protein intake on osteokines, bone turnover, and inflammatory markers in endurance athletes. Acute bouts of high-intensity running increase osteokines and bone turnover markers that promote bone resoprtion which parallels increases in pro-inflammatory markers in endurance athletes, suggesting crosstalk between these systems during and after exercise. Chronic endurance exercise promotes increased resting levels of bone formation, while reducing resting pro-inflammatory markers. Adequate dietary protein ingestion habitually and pre-, during, and post-exercise may attenuate bone resportion and pro-inflammatory markers in endurance athletes.
PURPOSE: This study aimed to investigate the association among liver fibrosis, physical activity, and bone mineral density in Korean adults.METHODS: Data from 8,019 participants aged 40–69 years in the 2008–2011 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed. Bone mineral density was measured using dual-energy X-ray bone densitometry (DXA). Liver fibrosis was defined using the fibrosis-4 (FIB-4) index. Physical activity was evaluated using the International Physical Activity Questionnaire (IPAQ). Logistic regression analysis was used to examine the associations among liver fibrosis, physical activity, and osteoporosis.RESULTS: Participants with liver fibrosis had a significantly higher risk of osteoporosis (OR=1.857, 95% CI=1.682-2.051, p <.001) compared to those without fibrosis. Similarly, physically inactive participants had a higher risk of osteoporosis (OR=1.392, 95% CI=1.273-1.523, p <.001) than physically active participants. After adjusting for age and sex, compared to the normal/active group (reference=1), the normal/inactive (OR=1.299, 95% CI=1.155-1.461, p <.001) and fibrosis/inactive groups (OR=1.243, 95% CI=1.058-1.461, p =.008) had a significantly higher risk of osteoporosis. Furthermore, after further adjustment for education, marital status, region, income, smoking, and chronic diseases, the association remained significant in the normal/inactive group (OR=1.279, 95% CI=1.137-1.439, p <.001) and fibrosis/inactive group (OR=1.216, 95% CI=1.033-1.431, p =.019). However, after further adjustment for body mass index, the association remained significant in the normal/inactive group (OR=1.213, 95% CI=1.074-1.370, p =.002).CONCLUSIONS: Our results suggest that physical activity is associated with the attenuation of the risk of osteoporosis associated with liver fibrosis. However, further studies are required to determine the relationship between other covariates and osteoporosis.
Background
: Older adults experience chronic inflammation, which is associated with health conditions such as sarcopenia, and resulting in reduced functional capacity. Resistance training (RT) is a beneficial intervention for improving health in the elderly.
Objective
: This study aimed to investigate the effect of RT on inflammatory biomarkers, body composition, and functional capacity in healthy adults aged 60 years and over. Additionally, this study conducted a meta-regression to investigate the moderating effect of exercise variables on inflammatory markers.
Method
: Medline, PubMed, Web of Science, Cochrane Library, Embase, and Google Scholar were searched systematically until December 2023. Randomized controlled trials (RCTs) assessing the impact of RT on C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), body weight, BMI, fat percentage, fat mass, lean mass, leg extension strength and six-minute walk test (6-MWT) were included. Effect size was estimated by using the mean difference (MD) with 95 % confidence interval (CI).
Results
: Nineteen RTCs involving 728 participants were included. The results revealed that CRP levels significantly decreased following RT programs (MD:0.74, p = 0.008), while TNF-α (MD: 0.1, p = 0.95) and IL-6 (MD:0.27, p = 0.12) did not show significant changes. Additionally, RT enhanced leg extension strength and 6-MWT performance.
Conclusion
: RT effectively reduces CRP concentrations and enhances functional capacity in healthy older adults. However, it does not have a significant impact on TNF-α and IL-6 levels. Future researches are needed to make a clear conclusion and understand the mechanisms underlying the effects of RT in healthy older adults.
Registration: The original protocol was registered (CRD42023487573) in PROSPERO database.
Inflammation serves as the body’s defensive mechanism against both external and internal entities that pose a threat to homeostasis. However, an excessive response, whether acute or chronic, in terms of either intensity or duration, can lead to damage to one’s own tissues. While acute inflammation is relatively easier and quicker to address, chronic inflammation is linked with long-term damage and persistent ailments that can reduce both the quality and duration of life. The aspects of chronic inflammation are often overlooked, making it even more crucial to pay attention to them. This chapter delves into the scientific evidence associating various factors with the risk of developing chronic inflammation, causing inflammatory pathologies. Additionally, we strive to present basic strategies, supported by scientific studies, that can be adopted to mitigate these risk factors.
High-density lipoprotein (HDL) is protective against cardiovascular disease. Exercise can increase HDL concentration, and some evidence suggests that this effect occurs more strongly in women than in men. Both HDL and exercise are associated with inflammation. We hypothesized a sex-by-exercise interaction on HDL level, whereby women would benefit from exercise more strongly than men, and tumor necrosis factor alpha and serum soluble tumor necrosis factor receptor-2 would mediate this relationship. This study included 2,957 older adult participants (1,520 women; 41% Black, 59% White; 73.6-years-old) from the Health, Aging, and Body Composition study. Regression models revealed a positive exercise-HDL relationship in women only (sex-by-exercise interaction: β = 0.09, p = .013; exercise on HDL in women: β = 0.07, p = .015), mediated by TNFα (axb = 0.15; CI: 0.01, 0.30), suggesting that exercise may increase HDL levels in women through reduced inflammation. Given that vascular risk contributes to Alzheimer’s disease risk, findings have implications for sex differences in AD risk factors.
Acute inflammation impairs vascular function in an age dependent manner and affects cardiovascular event risk. Regular aerobic exercise preserves vascular function with aging and potentially modifies how acute inflammation affects the vasculature. We hypothesize high cardiorespiratory fitness may accompany greater arterial responsiveness post-acute inflammation in older adults.
Preliminary assessment of the
prescribing errors in outpatient
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Background:
The Health, Aging and Body Composition (Health ABC) Study is a longitudinal cohort study started just over 25 years ago. This ground-breaking study tested specific hypotheses about the importance of weight, body composition and weight-related health conditions for incident functional limitation in older adults.
Methods:
Narrative review with analysis of ancillary studies, career awards, publications and citations.
Results:
Key findings of the study demonstrated the importance of body composition as a whole, both fat and lean mass, in the disablement pathway. The quality of the muscle in terms of its strength and its composition was found to be a critical feature in defining sarcopenia. Dietary patterns and especially protein intake, social factors and cognition were found to be critical elements for functional limitation and disability. The study is highly cited and its assessments have been widely adopted in both observational studies and clinical trials. Its impact continues as a platform for collaboration and career development.
Conclusions:
The Health ABC provides a knowledge base for the prevention of disability and promotion of mobility in older adults.
Atherosclerosis is a chronic disease whose first stages can begin in childhood. Obesity is one of the major risk factors for atherosclerosis, which is becoming an epidemic. The increase in prevalence of obesity has focused more attention on the relationship between obesity and atherosclerosis, and although the relationship between obesity and atherosclerosis has been widely reported, its potential mechanisms still need to be further elucidated. Salusins are a new class of bioactive peptides that play an important role as endogenous regulators of atherosclerosis process. Obesity is associated with a chronic inflammatory response characterized by abnormal adipokine production and activation of some pro-inflammatory signaling pathways. Past studies have shown that inflammatory process has a cause and effect relationship with obesity and cardiovascular diseases, including atherosclerosis. Also, arterial endothelial disorder is an early disorder in process of atherosclerosis, and presence of this disorder in obese children has been widely reported. The most important potential factor that will lead to obesity, inflammatory conditions and endothelial dysfunction is immobility. On the other hand, physical activity has wide health benefits and is considered as an important factor in primary and secondary prevention of cardiovascular diseases. Therefore, the current research seeks to investigate the role of physical activity in improving endogenous regulators of atherosclerosis in obese and sedentary children.
Health benefits of physical activity (PA) are well known; however, specific PA patterns that relate most strongly to cognitive aging outcomes are poorly understood. We characterized latent profiles of PA among older adults and examined associations with cognition and vascular burden. 124 functionally normal older adults wore a Fitbit™ for 30 days. Daily average step count, sedentary time (0 steps/min), and high-intensity time (≥120 steps/min) were calculated. Participants completed neurocognitive testing assessing cognitive domains of executive functioning and memory; medical history, from which vascular burden (i.e., a count of cardiovascular conditions) was calculated; and brain MRI (n = 44). Subgroups with similar PA patterns were identified via latent profile analysis. Three latent PA classes emerged: Class1Low PA (n = 49), Class2Average PA (n = 59), and Class3High-intensity PA (n = 16). PA class related to executive functioning and vascular burden, driven by better outcomes in Class3 than Class1. Sex-stratified analyses revealed these associations were strongest in males. Post hoc analyses showed a positive association between high-intensity PA and white matter integrity among males. High-intensity PA related to better cognitive and vascular health, particularly among males. Findings inform physical activity-specific and person-specific recommendations for optimal cognitive aging.
The COVID-19 pandemic compelled people to think about their physical and mental well-being. The current study investigates the relationship between exercise addiction (EA) and quality of life (QOL) through obsessive-compulsive disorder (OCD) and physiological symptoms. Correlation and mediation analyses were adopted to test the proposed models on 318 respondents. Two serial mediation models were examined between EA and QOL through OCD and physiological symptoms. Results revealed that there was a strong positive correlation between EA, OCD, and physiological symptoms with each other and a negative correlation between EA, OCD, and physiological symptoms with QOL. Individuals’ QOL was more affected by obsessive and compulsive traits rather than physiological injuries. This study elaborated on the understanding of EA and QOL specifically in a pandemic scenario.
Background:
This study examines the relationship between various domains of sedentary behavior and subsequent cognitive function to evaluate whether different sedentary activities have specific associations with future cognitive performance.
Methods:
Data were from 1,261 older adults participating in the Health, Aging and Body Composition (Health ABC) Study between 1999/2000 and 2006/2007. Total sitting time (h/day), reading time (h/week), and TV time (≤27/≥28 h/week) were self-reported at baseline and 3 years later. At follow-up, cognitive function was evaluated using the Teng Mini-Mental State Exam (3MS) and the Digit Symbol Substitution Test (DSST). Multivariable linear regression modeling examined the independent associations of baseline sedentary behaviors and 3-year change in those behaviors with cognitive function scores at follow-up, adjusting for important covariables.
Results:
Baseline total sitting time was positively associated with 3MS (β=0.14±0.07; p<0.05) and DSST (β=0.20±0.10; p<0.05) scores at follow-up, as was reading time (β=0.09±0.03; p<0.05 for 3MS score and β= 0.14± 0.04; p<0.01 for DSST score). Participants who increased their TV watching time over 3 years had a significantly lower 3MS score (β=-1.45±0.71; p<0.05) at follow-up, compared with those who maintained a low level of TV time (referent). These findings were independent of age, sex, race, education level, health status, depressive symptoms, and physical activity.
Conclusion:
Some types of sedentary behavior may have benefits for cognitive function in older age, thus highlighting the importance of measuring different domains of sitting time.
Background:
Diabetic nephropathy (DN) is a prevalent microvascular diabetic complication all over the world.
Objective:
This study was designed to measure oxidative stress, systemic inflammation and kidney function response to exercise training in patients with type 2 diabetic (T2DM) nephropathy.
Material and methods:
Eighty obese T2DM patients (50 males and 30 females), their body mass index (BMI) mean was 33.85±3.43 Kg/m2 and the mean of diabetes chronicity was 12.53±2.64 year participated in the present study and enrolled two groups; group I: received aerobic exercise training and group II: received no training intervention.
Results:
The mean values of creatinine, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) were significantly decreased, while the mean values of interleukin-10 (IL-10), glutathione peroxidase (GPx) and glutathione (GSH) were significantly increased in group (A) after the aerobic exercise training, however the results of the control group were not significant. In addition, there were significant differences between both groups at the end of the study (P<0.05).
Conclusion:
There is evidence that aerobic exercise training modulated oxidative stress and inflammatory cytokines and improved renal function among patients with diabetic nephropathy.
Vitamin D3 has a preventive, anti-inflammatory effect. However, there are still few studies linking the effects of athlete training to vitamin D3 supplementation and the immune response. The study evaluated the impact of vitamin D3 supplementation on interleukin 6 (IL-6) release during physical exercise in relation to C-reactive protein (CRP) levels in healthy male athletes. Twenty-five soccer players were divided into two groups-with (GS) and without (GN) vitamin D3 supplementation in a dose of 20,000 IU twice a week for 8 wk (about 6,000 IU/d). At the baseline (T1) and at the end (T2) of the training cycle serum concentrations of 25-hydroxyvitamin D [25(OH)D], IL-6 and CRP were measured. In the GS group, we observed a significant increase in 25(OH)D concentration (p=0.004), and non-significantly increased levels (p>0.05) of IL-6 and CRP. At the baseline, CRP in the supplemented athletes who had suboptimal vitamin D3 concentration in T1 (GSO) was significantly higher than in those with an optimal baseline vitamin D3 level (GO) (p=0.028). However, in GO in T2, a non-significant trend of negative correlation (p=0.055) between 25(OH)D concentration and IL-6 level was found. In the total study group (TG), a statistically significant (p=0.021) negative correlation in T1 was observed between 25(OH)D and CRP. However, our results do not support the immune-modulatory effect of vitamin D3 supplementation in a dose of 6,000 IU/d in athletes, in relation to IL-6 production and its subsequent stimulatory effect on CRP releasing.
With the increasing incidence of diabetic nephropathy (DN), there is an urgent need to find effective DN preventive and therapeutic modalities. It is widely believed that effective exercise is good for health. However, the beneficial role of exercise in kidney disease, especially in DN, and the underlying molecular mechanisms have rarely been reported. Muscle is not only an important motor organ but also an important endocrine organ, secreting a group of proteins called “myokines” into the blood circulation. Circulating myokines then move to various target organs to play different biological roles. In this review, we summarize the currently known myokines and the progress in research relating them to DN and discuss its potential as a therapeutic target for DN.
This chapter presents new scientific-based knowledge about the role of physical activity in the management and prevention of obesity-related inflammation.
Objective
The purpose of this study was to investigate the responses of selected inflammatory cytokines to isometric handgrip exercise and identify possible effects of intensity and duration of the isometric effort on these variables.
Methods
A total of 192 sedentary prehypertensive Nigerian participants aged between 30 and 50 years were recruited into the study and randomly distributed into 3 groups of 64 participants each. The participants performed 24 consecutive days of isometric handgrip exercise at 30% maximum voluntary contraction. At the end of the 24 days, group 1 discontinued the exercise protocol, while group 2 continued the exercise protocol for another 24 consecutive days, and group 3 continued with the exercise protocol for another 24 consecutive days but at 50% maximum voluntary contraction. The parameters used to assess the inflammatory cytokine variables included interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α).
Results
There was an increase in the resting values of IL-10 across the 3 groups, while the resting values of IL-6 and TNF-α were reduced significantly across groups. Generally, the exercise-induced changes in the levels of these cytokines (TNF-α, IL-6, and IL-10) should improve inflammatory and metabolic abnormalities.
Conclusion
The isometric handgrip exercise protocols in this study resulted in elevation of anti-inflammatory cytokine (IL-10) and reductions in the values of proinflammatory cytokines TNF- α and IL-6.
Background and Objectives
Although research on the health benefits of volunteering has proliferated, most studies are cross-sectional and rely on self-reported measures of health. Drawing from role theory, the objectives of this study are to examine if (1) volunteering engagement is related to systemic inflammation in later life, as measured by C-reactive protein (CRP), (2) the effect of volunteering varies by age and (3) volunteering is related to change in CRP over time.
Research Design and Methods
This study uses four waves of data from the Health and Retirement Study, a nationally representative survey of adults 50 years or older. Nested linear regression models were used to examine the relationship between volunteer engagement and CRP concentration in later life. Residualized regression models were used to examine the effects of volunteer engagement on change in CRP.
Results
Results revealed that volunteering is modestly associated with lower CRP concentration, but only for respondents 65+. Highly engaged volunteers had lower CRP than both mid-level and non-volunteers. Longitudinal analyses revealed a leveling of the beneficial effect of volunteering by age, indicative of reduced returns among the oldest respondents in our sample.
Discussion and Implications
These results support previous studies that volunteering, and doing so at a high engagement level, is associated with slightly lower levels of CRP. Leaders in medicine, public health, and social services should consider implementing volunteering programs for older adults.
Human adipose tissue expresses and releases the proinflammatory cytokine interleukin 6, potentially inducing low-grade systemic inflammation in persons with excess body fat.
To test whether overweight and obesity are associated with low-grade systemic inflammation as measured by serum C-reactive protein (CRP) level.
The Third National Health and Nutrition Examination Survey, representative of the US population from 1988 to 1994.
A total of 16616 men and nonpregnant women aged 17 years or older.
Elevated CRP level of 0.22 mg/dL or more and a more stringent clinically raised CRP level of more than 1.00 mg/dL.
Elevated CRP levels and clinically raised CRP levels were present in 27.6% and 6.7% of the population, respectively. Both overweight (body mass index [BMI], 25-29.9 kg/m2) and obese (BMI, > or =30 kg/m2) persons were more likely to have elevated CRP levels than their normal-weight counterparts (BMI, <25 kg/m2). After adjustment for potential confounders, including smoking and health status, the odds ratio (OR) for elevated CRP was 2.13 (95% confidence interval [CI], 1.56-2.91) for obese men and 6.21 (95% CI, 4.94-7.81) for obese women. In addition, BMI was associated with clinically raised CRP levels in women, with an OR of 4.76 (95% CI, 3.42-6.61) for obese women. Waist-to-hip ratio was positively associated with both elevated and clinically raised CRP levels, independent of BMI. Restricting the analyses to young adults (aged 17-39 years) and excluding smokers, persons with inflammatory disease, cardiovascular disease, or diabetes mellitus and estrogen users did not change the main findings.
Higher BMI is associated with higher CRP concentrations, even among young adults aged 17 to 39 years. These findings suggest a state of low-grade systemic inflammation in overweight and obese persons.
We developed a reproducible ELISA for C-reactive protein (CRP), calibrated with WHO Reference Material, for which intra- and interassay CVs were 3.0% and 6.0%, respectively. Analytical recovery was 97.9%. The distribution of CRP in a healthy blood donor population (n = 143) was nongaussian, with 2.5th, 50th, and 97.5th percentile values of 0.08, 0.64, and 3.11 mg/L, respectively. There was no sex-related difference, and the association with age was weak. In a study of variability [by the method of Fraser and Harris (Crit Rev Clin Lab Sci 1989;27:409-37)], the analytical variability was 5.2%; the within-subject variability, CVI, was 42.2%; and the between-subject variability, CVG, was 92.5%. The critical difference for sequential values significant at P < or =0.05 (i.e., the smallest percentage change unlikely to be due to analytical variability or CVI) was calculated as 118%, and the index of individuality, CVI/CVG, was 0.46. This suggests that CRP, like many clinical chemistry analytes, has limited usefulness in detecting early disease-associated changes when used in conjunction with a healthy reference interval. From a molecular epidemiological standpoint, the usefulness of CRP in longitudinal studies is suggested by the small index of individuality and by observations that (a) short-term fluctuations were infrequent, (b) all data stayed within the reference interval, and (c) relative rankings of the subjects over 6 months only moderately deteriorated.
Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis, and antagonism of TNF may reduce the activity of the disease. This study evaluated the safety and efficacy of a novel TNF antagonist - a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1 (TNFR:Fc).
In this multicenter, double-blind trial, we randomly assigned 180 patients with refractory rheumatoid arthritis to receive subcutaneous injections of placebo or one of three doses of TNFR:Fc (0.25, 2, or 16 mg per square meter of body-surface area) twice weekly for three months. The clinical response was measured by changes in composite symptoms of arthritis defined according to American College of Rheumatology criteria.
Treatment with TNFR:Fc led to significant reductions in disease activity, and the therapeutic effects of TNFR:Fc were dose-related. At three months, 75 percent of the patients in the group assigned to 16 mg of TNFR:Fc per square meter had improvement of 20 percent or more in symptoms, as compared with 14 percent in the placebo group (P<0.001). In the group assigned to 16 mg per square meter, the mean percent reduction in the number of tender or swollen joints at three months was 61 percent, as compared with 25 percent in the placebo group (P<0.001). The most common adverse events were mild injection-site reactions and mild upper respiratory tract symptoms. There were no dose-limiting toxic effects, and no antibodies to TNFR:Fc were detected in serum samples.
In this three-month trial TNFR:Fc was safe, well tolerated, and associated with improvement in the inflammatory symptoms of rheumatoid arthritis.
Increasing evidence demonstrates that atherosclerosis is an immunologically mediated disease in which the secretion of atherogenic and atheroprotective cytokines, by infiltrating blood mononuclear cells, plays an important role. It is not known whether long-term exercise alters this atherogenic and atheroprotective activity directly.
To determine the effect of long-term exercise on the atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease.
Before-after trial using a 6-month individualized, supervised exercise program, with an enrollment period from December 1996 to October 1997.
Hospital-based community wellness center.
Of 110 persons who responded to a public request for volunteers, 52 met the inclusion criteria (risk ratio for myocardial infarction > or =1.7 based on serum complement and/or C-reactive protein levels, and normal exercise treadmill test results). Forty-three of the 52 enrollees (25 women [mean age, 49.7 years] and 18 men [mean age, 48.1 years]) completed the study; 9 withdrew for personal reasons. Additional risk factors for ischemic heart disease included hypercholesterolemia (65.1 %), a family history of coronary heart disease (62.8%), inactivity (60.5%), hypertension (32.6%), obesity (25.6%), smoking (11.6%), and diabetes mellitus (4.7%).
Blood levels were compared at baseline and after the exercise program had been completed for the following: spontaneous and phytohemagglutinin-induced production of interleukin 1 alpha, tumor necrosis factor alpha, and interferon gamma (atherogenic cytokines), and interleukin 4, interleukin 10, and transforming growth factor beta 1 (atheroprotective cytokines) by blood mononuclear cells; lymphocyte phenotypes and mitogenic responses to phytohemagglutinin; and serum C-reactive protein levels.
Subjects exercised for a mean of 2.5 (range, 0.3-7.4) hours per week. Mononuclear cell production of atherogenic cytokines fell by 58.3 % (P<.001) following the exercise program, where as the production of atheroprotective cytokines rose by 35.9% (P<.001). Changes in transforming growth factor beta 1 and in phytohemagglutinin-induced atherogenic cytokine production after the exercise program were proportionate to the time subjects spent performing repetitive lower-body motion exercises (P<.02), indicating a dose-response relationship. After the exercise program, changes in cellular function were reflected systemically by a 35% decrease in serum levels of C-reactive protein (P=.12).
Our data suggest that long-term exercise decreases the atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease. This may be a mechanism whereby physical activity protects against ischemic heart disease.
To investigate in vivo adipose tissue production of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and their soluble receptors: TNF receptor type I (sTNFR-I), TNF receptor type II (sTNFR-II), and IL-6 receptor (sIL-6R), we determined arteriovenous differences in their levels across abdominal subcutaneous adipose tissue in obese subjects. Subjects had a median (interquartile range) age of 44.5 (27-51.3) yr, body mass index (BMI) of 32.9 (26. 0-46.6) kg/m(2), and %body fat of 42.5 (28.5-51.2) %. Although there was not a significant difference in the arteriovenous concentrations of TNF-alpha (P = 0.073) or sTNFR-II (P = 0.18), the levels of sTNFR-I (P = 0.002) were higher in the vein compared with artery, suggesting adipose tissue production of this soluble receptor. There was a significant arteriovenous difference in IL-6 (P < 0.001) but not in its soluble receptor (P = 0.18). There was no relationship between TNF-alpha levels and adiposity indexes (r(s) = 0.12-0.22, P = not significant); however, levels of both its soluble receptor isomers correlated significantly with BMI and %body fat (sTNFR-I r(s) = 0.42-0.72, P < 0.001; sTNFR-II r(s) = 0.36-0.65, P < 0.05- <0. 001). IL-6 levels correlated significantly with both BMI and %body fat (r(s) = 0.51, P = 0.004, and r(s) = 0.63, P < 0.001), but sIL-6R did not. In conclusion, 1) soluble TNFR-I is produced by adipose tissue, and concentrations of both soluble isoforms correlate with the degree of adiposity, and 2) IL-6, but not its soluble receptor, is produced by adipose tissue and relates to adiposity.
To assess the association of circulating levels of C-reactive protein, a sensitive systemic marker of inflammation, with different components of the metabolic syndrome.
Total cholesterol (TC), HDL cholesterol, triglycerides, uric acid, BMI , and prevalence of diabetes and hypertension were assessed in 747 men and 956 women aged 18-89 years who were participating in the population-based National Health and Nutrition Survey, which was carried out in former West Germany in 1987-1988.
There was a statistically significant positive crude correlation between C-reactive protein and TC (R = 0.19), TG (R = 0.29), BMI (R = 0.32), glucose (R = 0.11), and uric acid (R = 0.14) (all P < 0.0001). A negative correlation was found between C-reactive protein and HDL cholesterol (R = 0.13, P < 0.0001). The age-adjusted geometric means of C-reactive protein concentrations in subjects grouped according to the presence of 0-1, 2-3, and > or =4 features of the metabolic syndrome were 1.11, 1.27, and 2.16 mg/l, respectively, with a statistically highly significant trend (P < 0.0001).
The data suggest that a variety of features of the metabolic syndrome are associated with a systemic inflammatory response.
Higher levels of physical activity are associated with lower risk of cardiovascular disease. There is growing evidence that the development of the atherosclerotic plaque is associated with inflammation. In this study, the authors investigated the cross-sectional association between physical activity and markers of inflammation in a healthy elderly population. Data obtained in 1989-1990 and 1992-1993 from the Cardiovascular Health Study, a cohort of 5,888 men and women aged >/=65 years, were analyzed. Concentrations of the inflammation markers-C-reactive protein, fibrinogen, Factor VIII activity, white blood cells, and albumin-were compared cross-sectionally by quartile of self-reported physical activity. Compared with persons in the lowest quartile, those in the highest quartile of physical activity had 19%, 6%, 4%, and 3% lower concentrations of C-reactive protein, white blood cells, fibrinogen, and Factor VIII activity, respectively, after adjustment for gender, the presence of cardiovascular disease, age, race, smoking, body mass index, diabetes, and hypertension. Multivariate regression models suggested that the association of higher levels of physical activity with lower levels of inflammation markers may be mediated by body mass index and glucose. There was no association between physical activity and albumin. Higher levels of physical activity were associated with lower concentrations of four out of five inflammation markers in this elderly cohort. These data suggest that increased exercise is associated with reduced inflammation. Prospective studies will be required for verification of these findings.
Obese patients demonstrate a variety of biochemical, metabolic, and pulmonary abnormalities. Inflammatory mediators such as tumor necrosis factor-alpha and interleukin-6 (IL-6) may have a direct effect on glucose and lipid metabolism. Hypoxemia in itself induces release of IL-6. The aim of this study was to examine the relationship between IL-6 levels in healthy volunteers (control group) and three different groups of obese patients: patients without obstructive sleep apnea syndrome (OSAS), patients with OSAS, and patients with obesity hypoventilation syndrome (OHS) (daytime baseline oxygen saturation of <93%).
We measured serum IL-6 levels in 25 obese patients (body mass index of >35 kg/m2) and 12 healthy women.
The results demonstrate statistically significant differences in serum IL-6 levels between the control group (1.28 +/- 0.85 pg/mL) and obese patients without OSAS (7.69 +/- 5.06 pg/mL, p < 0.05) and with OSAS (5.58 +/- 0.37 pg/mL, p < 0.0005). In the patients with OHS, IL-6 concentrations were highest (43.13 +/- 24.27 pg/mL).
We conclude that serum IL-6 is increased in obese patients. The highest IL-6 levels were found in the patients with OHS.
There is increasing evidence that systemic inflammation and insulin resistance constitute interrelated events that contribute to atherosclerosis. We studied the effect of the association between circulating interleukin 6 (IL-6) levels, one of the major mediators of inflammation, and C-reactive protein on insulin resistance and blood pressure in 228 healthy volunteers.
The plasma IL-6 concentration was significantly and similarly associated with systolic (SBP) and diastolic (DBP) blood pressure, fasting insulin, and the fasting insulin resistance index (FIRI) in all subjects. When smokers were excluded from the analysis, plasma IL-6 levels correlated with percent fat mass (r = 0.19; P = 0.02), absolute fat mass (r = 0.17; P = 0.03), SBP, DBP, fasting insulin levels, and FIRI. The latter associations persisted after controlling for body mass index (r = 0.15 and r = 0.19; P = 0.02 and P = 0.0004 for SBP and DBP, respectively; r = 0.24 and r = 0.19, P = 0.004 and P = 0.03, for fasting insulin and FIRI, respectively).
Gender and smoking status significantly influenced the results. Although IL-6 levels were significantly associated with fasting insulin and FIRI in men, these significant correlations were not observed in women. Conversely, although IL-6 levels were significantly associated with SBP and DBP in women, these coefficients were not statistically significant in men. All of these associations were lost among smokers and remained significant in nonsmokers.
As IL-6 is the major mediator of the acute phase response by hepatocytes and induces the synthesis of C-reactive protein (CRP), we also controlled for the latter. Serum CRP levels correlated significantly with IL-6 in all the subjects, but mainly in nonsmokers and men. Of note was that this significant relationship was lost among smokers. CRP was associated with fasting insulin (r = 0.28; P < 0.0001) and FIRI (r = 0.25; P < 0.0001), but not with SBP or DBP (P = NS), in all subjects. Unlike IL-6, the associations between CRP and these parameters were similar in men and women and in smokers and nonsmokers. For insulin and FIRI they were stronger in women and in nonsmokers. CPR significantly correlated with the WHR only in men (r = 0.22; P = 0.01).
Using multiple linear regression in a stepwise manner to predict circulating IL-6 levels, smoking status (P = 0.0059) and FIRI (P = 0.03), but not fat mass or SBP, independently contributed to 11% of its variance in men. When CRP was introduced into the model, the latter (P < 0.0001) and smoking status (P = 0.02), but not FIRI, fat mass, or SBP, contributed to 33% of the variance in IL-6 levels. In women, only SBP (P = 0.04) contributed to 5% of its variance. When CRP was introduced into the model, again only SBP (P = 0.01) contributed to 10% of the variance in IL-6 levels.
In 25 of these subjects, insulin sensitivity was determined using the frequently sampled iv glucose tolerance test with minimal model analysis, and circulating IL-6 levels were strongly associated with the insulin sensitivity index (r = −0.65; P < 0.0001). Again, this relationship was even stronger in men (r =− 0.75; P < 0.001) and was not significant in women (r = −0.26; P = NS). In all of these subjects, only insulin sensitivity (P = 0.0037), not fat mass, contributed to 21% of the variance of IL-6 levels in a multiple linear regression analysis.
In summary, circulating IL-6 levels, by inducing either hypertension in women or insulin resistance in men, constitute a significant proatherogenic cytokine. The mechanisms of these associations should be further investigated.
Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus (DM); however, clinical data addressing this issue are limited.
To determine whether elevated levels of the inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) are associated with development of type 2 DM in healthy middle-aged women.
Prospective, nested case-control study.
The Women's Health Study, an ongoing US primary prevention, randomized clinical trial initiated in 1992.
From a nationwide cohort of 27 628 women free of diagnosed DM, cardiovascular disease, and cancer at baseline, 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls.
Incidence of confirmed clinically diagnosed type 2 DM by baseline levels of IL-6 and CRP.
Baseline levels of IL-6 (P<.001) and CRP (P<.001) were significantly higher among cases than among controls. The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 (95% confidence interval [CI], 3.7-15.4) and 15.7 for CRP (95% CI, 6.5-37.9). Positive associations persisted after adjustment for body mass index, family history of diabetes, smoking, exercise, use of alcohol, and hormone replacement therapy; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 (95% CI, 0.9-5.6; P for trend =.07) and 4.2 for CRP (95% CI, 1.5-12.0; P for trend =.001). Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c) of 6.0% or less and after adjustment for fasting insulin level.
Elevated levels of CRP and IL-6 predict the development of type 2 DM. These data support a possible role for inflammation in diabetogenesis.
Tumor necrosis factor-alpha (TNFalpha) plays an important role in the pathogenesis of insulin resistance and type 2 diabetes. Plasma levels of the soluble (s) fractions of TNFalpha receptors, especially sTNFR2, are good indicators of TNFalpha system activation in obesity. The aim of the present study was to assess the effect of exercise training on the TNFalpha system and to evaluate the relationship with changes in insulin sensitivity.
Sixteen obese women (body mass index (BMI)>27.8 kg/m(2)), 8 with normal (NGT) and 8 with impaired glucose tolerance (IGT), participated in an exercise training program which lasted for 12 weeks and included exercise performed on a bicycle ergometer at an individual intensity of 70% maximal heart rate, for 30 min, 5 days a week. Anthropometrical measurements and blood biochemical analyses were performed, and plasma TNFalpha, sTNFR1 and sTNFR2 levels were assessed. Insulin sensitivity was evaluated using the hyperinsulinemic euglycemic clamp technique (insulin infusion: 50 mU x kg(-1)xh(-1)).
At baseline, despite similar anthropometrical parameters, IGT subjects were markedly more insulin resistant and had higher TNFalpha and sTNFR2 concentrations. Exercise training increased insulin sensitivity and decreased TNFalpha and sTNFR2 levels, while sTNFR1 remained unchanged. The decrease in sTNFR2 was significantly related to the increase in insulin sensitivity; that relationship remained significant after adjustment for the concurrent changes in BMI, waist circumference, percentage of body fat, plasma glucose, insulin and free fatty acids.
Regular physical exercise decreases TNFalpha system activity and that decrease may be responsible for the concurrent increase in insulin sensitivity.
Physical activity has been associated with a reduced risk of coronary heart disease, but the mechanism underlying this association is unclear. Because coronary heart disease is increasingly seen as an inflammatory process, it might be reasonable to hypothesize that physical activity reduces risk of coronary heart disease by reducing or preventing inflammation.
The study examined the relationship between physical activity and elevated inflammation as indicated by a high C-reactive protein level, white blood cell count, or fibrinogen level. Study subjects were 3638 apparently healthy US men and women 40 years and older who participated in the Third National Health and Nutrition Examination Survey.
More frequent physical activity was independently associated with a lower odds of having an elevated C-reactive protein level. Compared with those engaging in physical activity 0 to 3 times per month, the odds of having an elevated C-reactive protein level was reduced among those engaging in physical activity 4 to 21 times per month (odds ratio, 0.77; 95% confidence interval, 0.58-1.02) and 22 or more times per month (odds ratio, 0.63; 95% confidence interval, 0.43-0.93) (P for trend,.02). Similar associations were seen for white blood cell count and fibrinogen levels.
More frequent physical activity is independently associated with a lower odds of having elevated inflammation levels among apparently healthy US adults 40 years and older, independent of several confounding factors. The results suggest that the association between physical activity and reduced coronary heart disease risk may be mediated by anti-inflammatory effects of regular physical activity.
To investigate in vivo adipose tissue production of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and their soluble receptors: TNF receptor type I (sTNFR-I), TNF receptor type II (sTNFR-II), and IL-6 receptor (sIL-6R), we determined arteriovenous differences in their levels across abdominal subcutaneous adipose tissue in obese subjects. Subjects had a median (interquartile range) age of 44.5 (27-51.3) yr, body mass index (BMI) of 32.9 (26.0-46.6) kg/m(2), and %body fat of 42.5 (28.5-51.2) %. Although there was not a significant difference in the arteriovenous concentrations of TNF-alpha (P = 0.073) or sTNFR-II (P = 0.18), the levels, of sTNFR-I (P = 0.002) were higher in the vein compared with artery, suggesting adipose tissue production of this soluble receptor., There was a significant arteriovenous difference in IL-6 (P < 0.001) but not in its soluble receptor (P = 0.18). There was no relationship between TNF-alpha levels and adiposity indexes (r(s) = 0.12-0.22, P = not significant); however, levels of both its soluble receptor isomers correlated significantly with BMI and %body fat (sTNFR-I r(s) = 0.42-0.72, P < 0.001; sTNFR-II r(s) = 0.3-0.65, P < 0.05- < 0.001). IL-6 levels correlated significantly with bath BMI and %body fat (r(s) = 0.51, P = 0.004, and r(s) = 0.63, P < 0.001), but sIL-6R did not. In conclusion, 1) soluble TNFR-I is produced by adipose tissue, and concentrations of both soluble isoforms correlate:with the degree of adiposity, and 2) IL-6, but not its soluble receptor, is produced by adipose tissue and relates to adiposity.
Background--Systemic chronic inflammation has been found to be related to all-cause mortality risk in older persons. We investigated whether specific chronic conditions, particularly cardiovascular disease (CVD), affect the association between high interleukin (IL)-6 level and mortality in a sample of disabled older women. Methods and Results--IL-6 serum level was measured at baseline in 620 women greater than or equal to 65 years old. The presence and severity of medical conditions was ascertained by standard criteria that used multiple sources of information. The sample was surveyed over the 3-year follow-up. After adjustment for potential confounders, compared with those in the lowest tertile, women in the highest IL-6 tertile were at higher risk of all-cause mortality. The presence of CVD, however, strongly affected the risk of mortality associated with high IL-6. Among women with prevalent CVD, those with high IL-6 levels had >4-fold risk of death (RR 4.6; 95% CI 2.0 to 10.5) compared with women in the lowest tertile, whereas the relative risk associated with high IL-6 among those without CVD was much lower and not significant (RR 1.8; 95% CI 0.7 to 4.2), Adjustment for all chronic diseases and disease severity measures, including ankle-brachial index, forced expiratory volume, and exercise tolerance, did not change the results. Conclusions--IL-6 level is helpful in identifying a subgroup of older CVD patients with high risk of death over a period of 3 years. Systemic inflammation, as measured by IL-6, may be related to the clinical evolution of older patients with CVD.
Context Increasing evidence demonstrates that
atherosclerosis is an immunologically mediated disease in which the
secretion of atherogenic and atheroprotective cytokines, by
infiltrating blood mononuclear cells, plays an important role. It is
not known whether long-term exercise alters this atherogenic and
atheroprotective activity directly.
Objective To determine the effect of long-term exercise on the
atherogenic activity of blood mononuclear cells in persons at risk of
developing ischemic heart disease.
Design Before-after trial using a 6-month individualized,
supervised exercise program, with an enrollment period from December
1996 to October 1997.
Setting Hospital-based community wellness center.
Participants Of 110 persons who responded to a public request for
volunteers, 52 met the inclusion criteria (risk ratio for myocardial
infarction ≥1.7 based on serum complement and/or C-reactive protein
levels, and normal exercise treadmill test results). Forty-three of the
52 enrollees (25 women [mean age, 49.7 years] and 18 men [mean age,
48.1 years]) completed the study; 9 withdrew for personal reasons.
Additional risk factors for ischemic heart disease included
hypercholesterolemia (65.1%), a family history of coronary heart
disease (62.8%), inactivity (60.5%), hypertension (32.6%), obesity
(25.6%), smoking (11.6%), and diabetes mellitus (4.7%).
Main Outcome Measures Blood levels were compared at
baseline and after the exercise program had been completed for the
following: spontaneous and phytohemagglutinin-induced production of
interleukin 1 α, tumor necrosis factor α, and interferon gamma
(atherogenic cytokines), and interleukin 4, interleukin 10, and
transforming growth factor beta 1 (atheroprotective cytokines) by blood
mononuclear cells; lymphocyte phenotypes and mitogenic responses to
phytohemagglutinin; and serum C-reactive protein levels.
Results Subjects exercised for a mean of 2.5 (range,
0.3-7.4) hours per week. Mononuclear cell production of atherogenic
cytokines fell by 58.3% (P<.001) following the exercise
program, whereas the production of atheroprotective cytokines rose by
35.9% (P<.001). Changes in transforming growth factor beta
1 and in phytohemagglutinin-induced atherogenic cytokine production
after the exercise program were proportionate to the time subjects
spent performing repetitive lower-body motion exercises
(P<.02), indicating a dose-response relationship. After the
exercise program, changes in cellular function were reflected
systemically by a 35% decrease in serum levels of C-reactive protein
(P=.12).
Conclusions Our data suggest that long-term exercise
decreases the atherogenic activity of blood mononuclear cells in
persons at risk of developing ischemic heart disease. This may be a
mechanism whereby physical activity protects against ischemic heart
disease.
C-reactive protein (CRP) is an ancient highly conserved molecule and a member of the pentraxin family of proteins. CRP is secreted by the liver in response to a variety of inflammatory cytokines. Levels of CRP increase very rapidly in response to trauma, inflammation, and infection and decrease just as rapidly with the resolution of the condition. Thus, the measurement of CRP is widely used to monitor various inflammatory states. CRP binds to damaged tissue, to nuclear antigens and to certain pathogenic organisms in a calcium-dependent manner. The function of CRP is felt to be related to its role in the innate immune system. Similar to immunoglobulin (Ig)G, it activates complement, binds to Fc receptors and acts as an opsonin for various pathogens. Interaction of CRP with Fc receptors leads to the generation of pro-inflammatory cytokines that enhance the inflammatory response. Unlike IgG, which specifically recognizes distinct antigenic epitopes, CRP recognizes altered self and foreign molecules based on pattern recognition. Thus, CRP is though to act as a surveillance molecule for altered self and certain pathogens. This recognition provides early defense and leads to a proinflammatory signal and activation of the humoural, adaptive immune system.
ACSM Position Stand on the Appropriate Intervention Strategies for Weight Loss and Prevention of Weight Regain for Adults. Med. Sci. Sports Exerc., Vol. 33, No. 12, 2001, pp. 2145–2156. In excess of 55% of adults in the United States are classified as either overweight (body mass index = 25–29.9 kg·m−2) or obese (body mass index ≥ 30 kg·m−2). To address this significant public health problem, the American College of Sports Medicine recommends that the combination of reductions in energy intake and increases in energy expenditure, through structured exercise and other forms of physical activity, be a component of weight loss intervention programs. An energy deficit of 500–1000 kcal·d−1 achieved through reductions in total energy intake is recommended. Moreover, it appears that reducing dietary fat intake to <30% of total energy intake may facilitate weight loss by reducing total energy intake. Although there may be advantages to modifying protein and carbohydrate intake, the optimal doses of these macronutritents for weight loss have not been determined. Significant health benefits can be recognized with participation in a minimum of 150 min (2.5 h) of moderate intensity exercise per week, and overweight and obese adults should progressively increase to this initial exercise goal. However, there may be advantages to progressively increasing exercise to 200–300 min (3.3–5 h) of exercise per week, as recent scientific evidence indicates that this level of exercise facilitates the long-term maintenance of weight loss. The addition of resistance exercise to a weight loss intervention will increase strength and function but may not attenuate the loss of fat-free mass typically observed with reductions in total energy intake and loss of body weight. When medically indicated, pharmacotherapy may be used for weight loss, but pharmacotherapy appears to be most effective when used in combination with modifications of both eating and exercise behaviors. The American College of Sports Medicine recommends that the strategies outlined in this position paper be incorporated into interventions targeting weight loss and the prevention of weight regain for adults.
Over the past several years, editors Chuck Corbin, Bob Pangrazi, and Don Franks have commissioned a series of articles about vital physical fitness and activity topics for The President’s Council on Physical Fitness and Sports Research Digest. Now collected in two compact volumes, these texts are designed to introduce a new audience to the important and timely contributions of these renowned experts in the field. Perfect for classroom or personal use, these important volumes provide students and professionals alike the foundation for a better understanding of the many dimensions of physical fitness and activity. This second volume contains 21 articles on such topics as the economic benefits of physical activity, physical activity and youth, motivating physical activity, and physical activity for special populations.
Adult mammals respond to tissue damage by implementing the acute phase response, which comprises a series of specific physiological reactions. This review outlines the principal cellular and molecular mechanisms that control initiation of the tissue response at the site of injury, the recruitment of the systemic defense mechanisms, the acute phase response of the liver and the resolution of the acute phase response.
In the present study, interleukin-6 (IL-6) and several acute phase proteins were measured in healthy participants (23-87 years of age). A linear correlation between IL-6 and age was established with an increase of 0.016 pg/ml (0.004) per year of life. Whereas CRP remained below 0.5 mg/dl in all participants, an increase with age for fibrinogen and an inverse relation for albumin as well as transferrin were obtained. However, the increase of IL-6 did not correlate with any of these changes. IL-6 associated diseases may therefore occur more often with advancing age, but in healthy participants IL-6 does not explain the changing plasma protein pattern resembling that of an acute phase reaction.
Inflammation and tissue injury elicit profound changes in the concentrations of several plasma proteins. These proteins are predominantly synthesized in the liver and named acute-phase proteins. The regulatory mechanisms that control this response are highly complex and include the release of various mediators affecting specific subsets of acute-phase genes. Individual mediators can either synergistically enhance or inhibit the effects of other mediators. Binding of mediators to their respective receptors on hepatocytes and transduction of this signal induce changes in acute-phase protein gene expression that are primarily regulated on a transcriptional level. However, under certain conditions post-transcriptional mechanisms may also be involved in this process. Although some acute-phase proteins have been shown to minimize tissue damage, as well as to participate in hemostasis, tissue repair, and regeneration in response to injury, the actual in vivo functions of several acute-phase reactants remain speculative. Measurements of acute-phase protein plasma concentrations can be of diagnostic or prognostic value under certain clinical conditions. Further characterization of the regulatory mechanisms that govern the acute-phase response in vivo could lead to the development of new therapeutic strategies aimed at improving the organism's integrated response to injury.
A coding scheme is presented for classifying physical activity by rate of energy expenditure, i.e., by intensity. Energy cost was established by a review of published and unpublished data. This coding scheme employs five digits that classify activity by purpose (i.e., sports, occupation, self-care), the specific type of activity, and its intensity as the ratio of work metabolic rate to resting metabolic rate (METs). Energy expenditure in kilocalories or kilocalories per kilogram body weight can be estimated for all activities, specific activities, or activity types. General use of this coding system would enhance the comparability of results across studies using self reports of physical activity.
In summary, available data demonstrate that IL-1 and TNF are the causative agents underlying the bone loss induced by estrogen deficiency. Indeed, these factors are produced in bone and the bone marrow, released in larger amounts from cells of estrogen-deficient subjects, and indispensable for reproducing the effects of estrogen deficiency in bone. These observations support the hypothesis that the bone sparing effect of estrogen is due to the ability of the hormone to block osteoclastogenesis, the activation of mature osteoclasts and, as recently demonstrated, the rate of apoptotic osteoclast death. Although IL-1 and TNF play a prominent causal role in these events, the bone-sparing effect of estrogen is mediated by numerous cytokines which, by simultaneously stimulating multiple target cells, induce effects that are not accounted for by any one single factor (Fig. 2). The ability of estrogen to regulate some, but not all, the cytokines involved in this process is not inconsistent with this hypothesis because cytokines have potent synergistic effects. Thus, a considerable increase in bone resorption may result from a relatively small increase in the concentration of only a few of the bone-resorbing factors present in the bone microenvironment. This concept is best illustrated by the study of Miyaura et al. demonstrating that the concentrations of either IL-1, IL-6, IL-6 receptor, or prostaglandins detected in the bone marrow of OVX mice are insufficient to account for the increased bone resorption caused by estrogen withdrawal. In contrast, the increase in bone resorption induced by OVX can be explained by the cumulative effects of these cytokines. Thus, a better understanding of the cooperative effects of cytokines and a recognition that the contribution of individual cytokines to postmenopausal bone loss varies with the passage of time after menopause are necessary to fully understand the mechanism of action of estrogen in bone. Although the relevance of individual bone-targeting cytokines in species specific, the development of transgenic mice with activatable or deactivatable promoters is likely to result in a further clarification of the integrated action of estrogen-regulated cytokines in human bone cells and lay the foundations for the use of cytokine inhibitors in the treatment of postmenopausal osteoporosis.
Markers of inflammation, such as C-reactive protein (CRP), are related to risk of cardiovascular disease (CVD) events in those with angina, but little is known about individuals without prevalent clinical CVD. We performed a prospective, nested case-control study in the Cardiovascular Health Study (CHS; 5201 healthy elderly men and women). Case subjects (n = 146 men and women with incident CVD events including angina, myocardial infarction, and death) and control subjects (n = 146) were matched on the basis of sex and the presence or absence of significant subclinical CVD at baseline (average follow-up, 2.4 years). In women but not men, the mean CRP level was higher for case subjects than for control subjects (P < or = .05). In general, CRP was higher in those with subclinical disease. Most of the association of CRP with female case subjects versus control subjects was in the subgroup with subclinical disease; 3.33 versus 1.90 mg/L, P < .05, adjusted for age and time of follow-up. Case-control differences were greatest when the time between baseline and the CVD event was shortest. The strongest associations were with myocardial infarction, and there was an overall odds ratio for incident myocardial infarction for men and women with subclinical disease (upper quartile versus lower three quartiles) of 2.67 (confidence interval [CI] = 1.04 to 6.81), with the relationship being stronger in women (4.50 [CI = 0.97 to 20.8]) than in men (1.75 [CI = 0.51 to 5.98]). We performed a similar study in the Rural Health Promotion Project, in which mean values of CRP were higher for female case subjects than for female control subjects, but no differences were apparent for men. Comparing the upper quintile with the lower four, the odds ratio for CVD case subjects was 2.7 (CI = 1.10 to 6.60). In conclusion, CRP was associated with incident events in the elderly, especially in those with subclinical disease at baseline.
Among apparently healthy men, elevated levels of C-reactive protein (CRP), a marker for systemic inflammation, predict risk of myocardial infarction and thromboembolic stroke. Whether increased levels of CRP are also associated with the development of symptomatic peripheral arterial disease (PAD) is unknown.
Using a prospective, nested, case-control design, we measured baseline levels of CRP in 144 apparently healthy men participating in the Physicians' Health Study who subsequently developed symptomatic PAD (intermittent claudication or need for revascularization) and in an equal number of control subjects matched on the basis of age and smoking habit who remained free of vascular disease during a follow-up period of 60 months. Median CRP levels at baseline were significantly higher among those who subsequently developed PAD (1.34 versus 0.99 mg/L; P=.04). Furthermore, the risks of developing PAD increased significantly with each increasing quartile of baseline CRP concentration such that relative risks of PAD from lowest (referent) to highest quartile of CRP were 1.0, 1.3, 2.0, and 2.1 (Ptrend=.02). Compared with those with no clinical evidence of disease, the subgroup of case patients who required revascularization had the highest baseline CRP levels (median= 1.75 mg/L; P= .04); relative risks from lowest to highest quartile of CRP for this end point were 1.0, 1.8, 3.8, and 4.1 (Ptrend=.02). Risk estimates were similar after additional control for body mass index, hypercholesterolemia, hypertension, diabetes, and a family history of premature atherosclerosis.
These prospective data indicate that among apparently healthy men, baseline levels of CRP predict future risk of developing symptomatic PAD and thus provide further support for the hypothesis that chronic inflammation is important in the pathogenesis of atherothrombosis.
In several white populations, visceral adipose tissue (VAT) is a risk factor for development of type 2 diabetes and dyslipidemia. VAT can be accurately assessed by computed topography or magnetic resonance imaging, but is also estimated from anthropometric variables, such as waist-to-hip ratio, waist circumference, or sagittal diameter. To date, anthropometric variables have been used largely in whites and inadequate data are available to evaluate the validity of these variables in other groups.
The objectives of this study were to 1) determine whether amount of VAT in relation to total body fatness differs in different race and sex groups and 2) determine which anthropometric variables predict amount of VAT in different race and sex groups.
We determined the amount and location of body fat, including assessment of VAT by computed tomography, in young adult white and black men and women participating in the 10-y follow-up of the CARDIA (Coronary Artery Risk Development in Young Adults) Study.
Black men had less visceral fat (73.1+/-35.9 cm2) than white men (99.3+/-40 cm2), even when VAT was corrected for total body fatness. Black women were more obese than white women and thus had more visceral fat (75.1+/-37.5 compared with 58.6+/-35.9 cm2, respectively). This difference disappeared when corrected for total body fatness.
Both waist circumference and sagittal diameter were good predictors of VAT in all groups. However, the nature of this relation differed such that race- and sex-specific equations will likely be required to estimate VAT from waist circumference or sagittal diameter.
To investigate whether interleukin-6 and C-reactive protein levels predict all-cause and cause-specific mortality in a population-based sample of nondisabled older people.
A sample of 1,293 healthy, nondisabled participants in the Iowa 65+ Rural Health Study was followed prospectively for a mean of 4.6 years. Plasma interleukin-6 and C-reactive protein levels were measured in specimens obtained from 1987 to 1989.
Higher interleukin-6 levels were associated with a twofold greater risk of death [relative risk (RR) for the highest quartile (> or = 3.19 pg/mL) compared with the lowest quartile of 1.9 [95% confidence interval, CI, 1.2 to 3.1]). Higher C-reactive protein levels (> or = 2.78 mg/L) were also associated with increased risk (RR = 1.6; CI, 1.0 to 2.6). Subjects with elevation of both interleukin-6 and C-reactive protein levels were 2.6 times more likely (CI, 1.6 to 4.3) to die during follow-up than those with low levels of both measurements. Similar results were found for cardiovascular and noncardiovascular causes of death, as well as when subjects were stratified by sex, smoking status, and prior cardiovascular disease, and for both early (<2.3 years) and later follow-up. Results were independent of age, sex, body mass index, and history of smoking, diabetes, and cardiovascular disease, as well as known indicators of inflammation including fibrinogen and albumin levels and white blood cell count.
Higher circulating levels of interleukin-6 and C-reactive protein were associated with mortality in this population-based sample of healthy older persons. These measures may be useful for identification of high-risk subgroups for anti-inflammatory interventions.
The serum concentration of interleukin 6 (IL-6), a cytokine that plays a central role in inflammation, increases with age. Because inflammation is a component of many age-associated chronic diseases, which often cause disability, high circulating levels of IL-6 may contribute to functional decline in old age. We tested the hypothesis that high levels of IL-6 predict future disability in older persons who are not disabled.
Participants at the sixth annual follow-up of the Iowa site of the Established Populations for Epidemiologic Studies of the Elderly aged 71 years or older were considered eligible for this study if they had no disability in regard to mobility or in selected activities of daily living (ADL), and they were re-interviewed 4 years later. Incident cases of mobility-disability and of ADL-disability were identified based on responses at the follow-up interview. Measures of IL-6 were obtained from specimens collected at baseline from the 283 participants who developed any disability and from 350 participants selected randomly (46.9%) from those who continued to be non-disabled.
Participants in the highest IL-6 tertile were 1.76 (95% CI, 1.17-2.64) times more likely to develop at least mobility-disability and 1.62 (95% CI, 1.02-2.60) times more likely to develop mobility plus ADL-disability compared with to the lowest IL-6 tertile. The strength of this association was almost unchanged after adjusting for multiple confounders. The increased risk of mobility-disability over the full spectrum of IL-6 concentration was nonlinear, with the risk rising rapidly beyond plasma levels of 2.5 pg/mL.
Higher circulating levels of IL-6 predict disability onset in older persons. This may be attributable to a direct effect of IL-6 on muscle atrophy and/or to the pathophysiologic role played by IL-6 in specific diseases.
An intense physical exercise induces an inflammatory reaction as demonstrated by the delayed increase in blood of acute phase proteins and among them of C-reactive protein (CRP). There is also evidence for a diminished acute phase reaction due to regular exercise suggesting a suppression of the inflammatory response through training. With this background CRP was measured by a sensitive enzyme immunoassay under resting conditions before and after 9 months of training in 14 subjects preparing for a marathon with the aim of studying the effect of training on the base-line CRP concentration. The mean distance run per week increased significantly from 31 +/- 9 km at the beginning to 53 +/- 15 km after 8 months of training (p < 0.01). The aerobic capacity rose significantly after training as demonstrated by the increase of running velocity during a maximal treadmill test from 3.82 +/- 0.29 m/s pre-training to 4.17 +/- 0.17 m/s post-training at a blood lactate concentration of 4 mmol/L (p < 0.01). In 10 of 12 runners base-line CRP was diminished after training in spite of a continuous increase of training intensity. The CRP median fell from 1.19 mg/L before to 0.82 mg/L after training (p < 0.05). Since intense physical exercise is known to be associated with an inflammatory reaction of muscles and tendons, the CRP decrease was unexpected. In 2 subjects the CRP concentration rose markedly because of a borrelia infection and a knee injury, respectively. These values were caused by a pathological condition and were not considered for the statistical evaluation. In 10 non-training control subjects the CRP median did not change significantly during the same 9 months period. The decrease of the CRP base-line concentration after training suggests that intensive regular exercise has a systemic anti-inflammatory effect. This is of particular interest with regard to several recent reports confering on the concentration of CRP in plasma a predictive value for the risk of cardiac infarction, venous thrombosis or stroke.
Since inflammation is believed to have a role in the pathogenesis of cardiovascular events, measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events.
We conducted a prospective, nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation. The markers included high-sensitivity C-reactive protein (hs-CRP), serum amyloid A, interleukin-6, and soluble intercellular adhesion molecule type 1 (sICAM-1). We also studied homocysteine and a variety of lipid and lipoprotein measurements. Cardiovascular events were defined as death from coronary heart disease, nonfatal myocardial infarction or stroke, or the need for coronary-revascularization procedures.
Of the 12 markers measured, hs-CRP was the strongest univariate predictor of the risk of cardiovascular events; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 (95 percent confidence interval, 2.2 to 8.9). Other markers significantly associated with the risk of cardiovascular events were serum amyloid A (relative risk for the highest as compared with the lowest quartile, 3.0), sICAM-1 (2.6), interleukin-6 (2.2), homocysteine (2.0), total cholesterol (2.4), LDL cholesterol (2.4), apolipoprotein B-100 (3.4), HDL cholesterol (0.3), and the ratio of total cholesterol to HDL cholesterol (3.4). Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone (P<0.001). The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter (3.4 mmol per liter), the target for primary prevention established by the National Cholesterol Education Program. In multivariate analyses, the only plasma markers that independently predicted risk were hs-CRP (relative risk for the highest as compared with the lowest quartile, 1.5; 95 percent confidence interval, 1.1 to 2.1) and the ratio of total cholesterol to HDL cholesterol (relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.9).
The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events.
The anti-inflammatory cytokines are a series of immunoregulatory molecules that control the proinflammatory cytokine response. Cytokines act in concert with specific cytokine inhibitors and soluble cytokine receptors to regulate the human immune response. Their physiologic role in inflammation and pathologic role in systemic inflammatory states are increasingly recognized. Major anti-inflammatory cytokines include interleukin (IL)-1 receptor antagonist, IL-4, IL-6, IL-10, IL-11, and IL-13. Specific cytokine receptors for IL-1, tumor necrosis factor-alpha, and IL-18 also function as proinflammatory cytokine inhibitors. The nature of anti-inflammatory cytokines and soluble cytokine receptors is the focus of this review. The current and future therapeutic uses of these anti-inflammatory cytokines are also reviewed.
Interleukin-6 (IL-6) plays a central role in inflammation and tissue injury. However, epidemiological data evaluating the role of IL-6 in atherogenesis are sparse.
In a prospective study involving 14 916 apparently healthy men, we measured baseline plasma concentration of IL-6 in 202 participants who subsequently developed myocardial infarction (MI) and in 202 study participants matched for age and smoking status who did not report vascular disease during a 6-year follow-up. Median concentrations of IL-6 at baseline were higher among men who subsequently had an MI than among those who did not (1.81 versus 1. 46 pg/mL; P=0.002). The risk of future MI increased with increasing quartiles of baseline IL-6 concentration (P for trend <0.001) such that men in the highest quartile at entry had a relative risk 2.3 times higher than those in the lowest quartile (95% CI 1.3 to 4.3, P=0.005); for each quartile increase in IL-6, there was a 38% increase in risk (P=0.001).This relationship remained significant after adjustment for other cardiovascular risk factors, was stable over long periods of follow-up, and was present in all low-risk subgroups, including nonsmokers. Although the strongest correlate of IL-6 in these data was C-reactive protein (r=0.43, P<0.001), the relationship of IL-6 with subsequent risk remained after control for this factor (P<0.001).
In apparently healthy men, elevated levels of IL-6 are associated with increased risk of future MI. These data thus support a role for cytokine-mediated inflammation in the early stages of atherogenesis.
C-reactive protein (CRP) is an ancient highly conserved molecule and a member of the pentraxin family of proteins. CRP is secreted by the liver in response to a variety of inflammatory cytokines. Levels of CRP increase very rapidly in response to trauma, inflammation, and infection and decrease just as rapidly with the resolution of the condition. Thus, the measurement of CRP is widely used to monitor various inflammatory states. CRP binds to damaged tissue, to nuclear antigens and to certain pathogenic organisms in a calcium-dependent manner. The function of CRP is felt to be related to its role in the innate immune system. Similar to immunoglobulin (Ig)G, it activates complement, binds to Fc receptors and acts as an opsonin for various pathogens. Interaction of CRP with Fc receptors leads to the generation of proinflammatory cytokines that enhance the inflammatory response. Unlike IgG, which specifically recognizes distinct antigenic epitopes, CRP recognizes altered self and foreign molecules based on pattern recognition. Thus, CRP is though to act as a surveillance molecule for altered self and certain pathogens. This recognition provides early defense and leads to a proinflammatory signal and activation of the humoural, adaptive immune system.
To evaluate the effects of moderate-intensity regular exercise on serum levels of tumor necrosis factor-alpha (TNF-alpha) and glucose and lipid metabolism parameters.
Longitudinal intervention study of a 5 month exercise training program (30-45 min/day, 4-5 days/week).
Forty-one healthy Japanese women aged 41-69 y at baseline; 27 participants in the exercise program.
Body mass index (BMI), waist-to-hip ratio (WHR), percentage body fat, and fasting levels for serum TNF-alpha, serum soluble TNF receptor p55 (TNF-RI) and TNF receptor p75 (TNF-RII), serum lipids, HbA1c, and serum insulin before and after exercise.
In overweight to obese subjects, serum levels of TNF-alpha, TNF-RI and TNF-RII were significantly higher than those in lean subjects. There were significant correlations between log serum TNF-alpha and BMI, percentage body fat, WHR, HbA1c and log insulin. TNF-RI was significantly correlated with BMI, percentage body fat, WHR and HbA1c. TNF-RII was also associated with BMI, percentage body fat and WHR. However, the correlation between TNF-RII and HbA1c did not reach statistical significance. Neither TNF-RI nor TNF-RII was correlated with log insulin. In contrast, TNF-alpha, TNF-RI and TNF-RII were negatively correlated with HDL cholesterol. Regular exercise decreased BMI, percentage body fat, HbA1c, serum TNF-alpha, TNF-RI and TNF-RII and increased HDL cholesterol levels. In addition, exercise-induced change in serum TNF-alpha was independently correlated with changes in HbA1c and serum insulin, after being adjusted for the change in fat-free mass.
Changes in serum TNF-alpha that occur with exercise may play an important role in improving glucose metabolism parameters.
Chronic inflammation has been proposed as a biological mechanism underlying the decline in physical function that occurs with aging. The purpose of this investigation was to examine the cross-sectional and prospective relationships between markers of inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), with several measures of physical performance in older persons aged 70 to 79 years.
Subjects were 880 high-functioning men and women participating in the MacArthur Study of Successful Aging (n = 1189), a subset of the Established Populations for Epidemiologic Studies of the Elderly (n = 4030). Plasma IL-6 and CRP levels were determined by enzyme-linked immunosorbent assay and log transformed to normalize the distributions. Physical function measures included handgrip strength, signature time, chair stands (time to complete five repetitions), and 6-m walk time.
Women had lower (p < .05) IL-6 levels than men, but there was no significant difference between blacks and whites. IL-6 and CRP levels were higher (p < .05) in current smokers than in nonsmokers and in those with a greater body mass index (BMI). Hours per year undertaking moderate and strenuous physical activity were also related to inflammatory markers with higher (p < .001) IL-6 and CRP levels in less active individuals. After adjusting for age, sex, race, BMI, smoking status, use of nonsteroidal anti-inflammatory drugs, and prevalence of morbidity, those in the top two quartiles for walking speed had lower (p = .012) IL-6 levels than those in the bottom quartile. In addition, there was a trend (p = .038) for lower CRP levels in those with higher walking speed. CRP levels were also lower (p = .04) in individuals in the top quartile for grip strength. No significant differences were noted for chair stands or signature time performance. Repeat performance measures obtained on 405 subjects (67% of those eligible at baseline) obtained 7 years later had declined significantly (grip strength, 18%; signature time, 21%; walking speed, 31%; p < .001), except for the chair rise; however, baseline IL-6 and CRP were not associated with a change in performance. However, those who died or who were unable to undergo testing had higher baseline IL-6 and CRP levels (p < .01) and slower walking speed (p < .05).
Although IL-6 has been shown to predict onset of disability in older persons and both IL-6 and CRP are associated with mortality risk, these markers of inflammation have only limited associations with physical performance, except for walking measures and grip strength at baseline, and do not predict change in performance 7 years later in a high-functioning subset of older adults.
Systemic chronic inflammation has been found to be related to all-cause mortality risk in older persons. We investigated whether specific chronic conditions, particularly cardiovascular disease (CVD), affect the association between high interleukin (IL)-6 level and mortality in a sample of disabled older women.
IL-6 serum level was measured at baseline in 620 women >/=65 years old. The presence and severity of medical conditions was ascertained by standard criteria that used multiple sources of information. The sample was surveyed over the 3-year follow-up. After adjustment for potential confounders, compared with those in the lowest tertile, women in the highest IL-6 tertile were at higher risk of all-cause mortality. The presence of CVD, however, strongly affected the risk of mortality associated with high IL-6. Among women with prevalent CVD, those with high IL-6 levels had >4-fold risk of death (RR 4.6; 95% CI 2.0 to 10.5) compared with women in the lowest tertile, whereas the relative risk associated with high IL-6 among those without CVD was much lower and not significant (RR 1.8; 95% CI 0.7 to 4.2). Adjustment for all chronic diseases and disease severity measures, including ankle-brachial index, forced expiratory volume, and exercise tolerance, did not change the results.
IL-6 level is helpful in identifying a subgroup of older CVD patients with high risk of death over a period of 3 years. Systemic inflammation, as measured by IL-6, may be related to the clinical evolution of older patients with CVD.
Cytokines are soluble glycoproteins that are produced by and mediate communication between and within immune and nonimmune cells, organs and organ systems throughout the body. Pro- and anti-inflammatory mediators constitute the inflammatory cytokines, which are modulated by various stimuli, including physical activity, trauma and infection. Physical activity affects local and systemic cytokine production at different levels, often exhibiting striking similarity to the cytokine response to trauma and infection.
The present review examines the cytokine response to short term exercise stress, with an emphasis on the balance between pro- and anti-inflammatory mechanisms and modulation of both innate and specific immune parameters through cytokine regulation. The effects of long term exercise on cytokine responses and the possible impact on various facets of the immune system are also discussed, with reference to both cross-sectional and longitudinal studies of exercise training. Finally, the validity of using exercise as a model for trauma and sepsis is scrutinised in the light of physiological changes, symptomatology and outcome, and limitations of the model are addressed.
Further studies, examining the effect of exercise, trauma and infection on novel cytokines and cytokine systems are needed to elucidate the significance of cytokine regulation by physical activity and, more importantly, to clarify the health implications of short and long term physical activity with respect to overall immune function and resistance to infection.
The response of the body to a cancer is not a unique mechanism but has many parallels with inflammation and wound healing. This article reviews the links between cancer and inflammation and discusses the implications of these links for cancer prevention and treatment. We suggest that the inflammatory cells and cytokines found in tumours are more likely to contribute to tumour growth, progression, and immunosuppression than they are to mount an effective host antitumour response. Moreover cancer susceptibility and severity may be associated with functional polymorphisms of inflammatory cytokine genes, and deletion or inhibition of inflammatory cytokines inhibits development of experimental cancer. If genetic damage is the "match that lights the fire" of cancer, some types of inflammation may provide the "fuel that feeds the flames". Over the past ten years information about the cytokine and chemokine network has led to development of a range of cytokine/chemokine antagonists targeted at inflammatory and allergic diseases. The first of these to enter the clinic, tumour necrosis factor antagonists, have shown encouraging efficacy. In this article we have provided a rationale for the use of cytokine and chemokine blockade, and further investigation of non-steroidal anti-inflammatory drugs, in the chemoprevention and treatment of malignant diseases.
Cytokines appear to be major regulators of adipose tissue metabolism. Therapeutic modulation of cytokine systems offers the possibility of major changes in adipose tissue behaviour. Cytokines within adipose tissue originate from adipocyte, preadipocyte and other cell types. mRNA expression studies show that adipocytes can synthesise both tumour necrosis factor alpha (TNF-alpha) and several interleukins (IL), notably IL-1beta and IL-6. Other adipocyte products with 'immunological' actions include complement system products and macrophage colony-stimulating factor. Cytokine secretion within adipocytes appears similar to that of other cells. There is general agreement that circulating TNF-alpha and IL-6 concentrations are mildly elevated in obesity. Most studies suggest increased TNF-alpha mRNA expression or secretion in vitro in adipose tissue from obese subjects. The factors regulating cytokine release within adipose tissue appear to include usual 'inflammatory' stimuli such as lipopolysaccaride, but also the size of the fat cells per se and catecholamines. There is conflicting data about whether insulin and cortisol regulate TNF-alpha. The effects of cytokines within adipose tissue include some actions that might be characterised as metabolic. TNF-alpha and IL-6 inhibit lipoprotein lipase, and TNF-alpha additionally stimulates hormone-sensitive lipase and induces uncoupling protein expression. TNF-alpha also down regulates insulin-stimulated glucose uptake via effects on glucose transporter 4, insulin receptor autophosphorylation and insulin receptor substrate-1. All these effects will tend to reduce lipid accumulation within adipose tissue. Other effects appear more 'trophic', and include the induction of apoptosis, regulation of cell size and induction of de-differentiation (the latter involving reduced peroxisome proliferator-activated receptor gamma). Cytokines are important stimulators and repressors of other cytokines. In addition, cytokines appear to modulate other regulatory systems. Examples of the latter include effects on leptin secretion (probably stimulation followed by inhibition) and reduction of beta3-adrenoceptor expression. There seems to be no clear agreement as to which cytokines derived from adipose tissue act as remote regulators, i.e. hormones. Leptin, which is structurally a cytokine, is also a hormone. IL-6 appears to be released systemically by adipose tissue, but TNF-alpha is probably not. Both leptin and IL-6 appear to act on the hypothalamus, IL-6 acts on the liver, while leptin may have actions on the pancreas. The importance of the immune system in whole-body energy balance provides a rationale for the links between cytokines and adipose tissue. It seems clear that TNF-alpha is a powerful autocrine and paracrine regulator of adipose tissue. Other cytokines, notably leptin, and possibly IL-6, have lesser actions on adipose tissue. These cytokines act as hormones, reporting the state of adipose tissue stores throughout the body.
In excess of 55% of adults in the United States are classified as either overweight (body mass index = 25-29.9 kg.m(-2)) or obese (body mass index > or = 30 kg.m(-2)). To address this significant public health problem, the American College of Sports Medicine recommends that the combination of reductions in energy intake and increases in energy expenditure, through structured exercise and other forms of physical activity, be a component of weight loss intervention programs. An energy deficit of 500-1000 kcal.d-1 achieved through reductions in total energy intake is recommended. Moreover, it appears that reducing dietary fat intake to <30% of total energy intake may facilitate weight loss by reducing total energy intake. Although there may be advantages to modifying protein and carbohydrate intake, the optimal doses of these macronutritents for weight loss have not been determined. Significant health benefits can be recognized with participation in a minimum of 150 min (2.5 h) of moderate intensity exercise per week, and overweight and obese adults should progressively increase to this initial exercise goal. However, there may be advantages to progressively increasing exercise to 200-300 min (3.3-5 h) of exercise per week, as recent scientific evidence indicates that this level of exercise facilitates the long-term maintenance of weight loss. The addition of resistance exercise to a weight loss intervention will increase strength and function but may not attenuate the loss of fat-free mass typically observed with reductions in total energy intake and loss of body weight. When medically indicated, pharmacotherapy may be used for weight loss, but pharmacotherapy appears to be most effective when used in combination with modifications of both eating and exercise behaviors. The American College of Sports Medicine recommends that the strategies outlined in this position paper be incorporated into interventions targeting weight loss and the prevention of weight regain for adults.
Physical activity is associated with lower risk of cardiovascular disease, but the mechanisms are uncertain. Hemostatic and inflammatory markers have been linked with risk of cardiovascular disease. We therefore examined the relationship between physical activity and hemostatic and inflammatory variables.
In 1998 to 2000, 20 years after the initial screening of 7735 men 40 to 59 years old from general practices in 24 British towns, 4252 subjects (77% of available survivors, now 60 to 79 old) attended for reexamination. A fasting blood sample was available in 4088 men. All men on warfarin (n=134) and men with incomplete data on physical activity (n=144) were excluded, leaving 3810 men for analysis. Physical activity showed a significant and inverse dose-response relationship with fibrinogen, plasma and blood viscosity, platelet count, coagulation factors VIII and IX, von Willebrand factor, fibrin D-dimer, tissue plasminogen activator antigen, C-reactive protein, and white cell count, even after adjustment for possible confounders. The effects were similar in men with and without prevalent cardiovascular disease. No relationship was seen with activated partial thromboplastin time, activated protein C resistance, hematocrit, or factor VII. An examination of changes in physical activity between baseline and 20 years later showed that inactive men who took up at least light physical activity had levels of blood variables approaching those who remained at least lightly active. Those who became inactive showed levels more similar to those who remained inactive.
These data suggest that the benefit of physical activity on cardiovascular disease may be at least partly a result of effects on hemostasis and inflammation.
Elevated C-reactive protein (CRP) is associated with increased coronary heart disease (CHD) risk. Cardiorespiratory fitness ("fitness") is related with lower CHD risk; however, its relationship with CRP is relatively unknown.
Cross-sectional associations between fitness and plasma CRP were examined among 135 African American (AA), Native American (NA), and Caucasian (CA) women (55+/-11 year; 28+/-6 kg/m2). Fitness was assessed with a maximal treadmill exercise test. Plasma CRP concentrations were determined with the Dade Behring high-sensitivity immunoassay. Geometric mean CRP levels were 0.43, 0.25, and 0.23 mg/dL, and average maximal MET levels of fitness were 7.2, 9.1, and 10 METs for AA, NA, and CA, respectively. CRP decreased across tertiles of fitness (P=0.002), increased across tertiles of BMI (P=0.0007), and varied by race (P=0.002). After adjustment for covariates, lower CRP (P<0.05) was observed across tertiles of fitness among NA and CA, but not AA. Among all women, after adjusting for race and covariates, the odds of high-risk CRP (>0.19 mg/dL) were 0.67 (95% CI=0.19 to 2.4) among fit (>6.5 METs) versus unfit women.
The health benefits from enhanced fitness may have an antiinflammatory mechanism.
Physical activity may lower the risk for coronary heart disease by mitigating inflammation, which plays a key role in the pathophysiology of atherosclerosis. The purpose of this study was to examine the association between physical activity and C-reactive protein concentration in a national sample of the U.S. population.
The analytic sample included 13,748 participants >or=20 years of age in the National Health and Nutrition Examination Survey III (1988-1994) with complete data for the main study variables.
After adjusting for age, sex, ethnicity, education, work status, smoking status, cotinine concentration, hypertension, body mass index, waist-to-hip ratio, high-density lipoprotein cholesterol concentration, and aspirin use, the odds ratios for elevated C-reactive protein concentration (dichotomized at the >or=85th percentile of the sex-specific distribution) were 0.98 (95% confidence interval = 0.78-1.23), 0.85 (0.70-1.02), and 0.53 (0.40-0.71) for participants who engaged in light, moderate, and vigorous physical activity, respectively, during the previous month compared with participants who did not engage in any leisure-time physical activity. In addition, leisure-time physical activity was positively associated with serum albumin concentration and inversely associated with both log-transformed plasma fibrinogen concentration and log-transformed white blood cell count.
These results add to mounting evidence that physical activity may reduce inflammation, which is a critical process in the pathogenesis of cardiovascular disease.
Interleukin-6 (IL-6) and C-reactive protein (CRP) are markers of systemic vascular inflammation that herald atherothrombosis and may have important interrelationships with traditional cardiovascular risk factors.
We conducted a cross-sectional analysis among 340 apparently healthy women enrolled in the Women's Health Study. In unadjusted analyses, higher levels of IL-6 and CRP were seen with increasing body mass index (BMI), systolic and diastolic blood pressure, and smoking exposure. IL-6 levels were related to the frequency of alcohol intake (P=0.002) and showed an inverse relationship with exercise frequency and hormone replacement therapy (P<0.0001 for both). CRP levels increased with hormone replacement therapy (P=0.0002). Associations among IL-6, CRP, and lipid levels were minimal. Overall, mean levels of IL-6 and CRP increased with increasing numbers of clinical risk factors (P<0.0001). In multivariate analyses, independent relationships were seen between levels of IL-6 and age, BMI, smoking, systolic blood pressure, alcohol use, presence of diabetes, and frequency of exercise. CRP was associated with age, BMI, systolic blood pressure, high density lipoprotein, smoking, and hormone replacement therapy in adjusted analyses.
Plasma levels of IL-6 and CRP are independently related to several clinical cardiovascular risk factors in women.
C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women
- Hennekens C Buring
Ridker P, Hennekens C, Buring J et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836–843.
Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women
- Fernandez-Real
C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women
- Ridker
Pro-inflammatory cytokines and adipose tissue
- Coppack
Variability in the measurement of C‐reactive protein in healthy subjects
- Macy E