ArticleLiterature Review

Exercise, Inflammation, and Innate Immunity

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Abstract

Regular exercise is protective against several chronic diseases ranging from physiologic diseases such as cardiovascular disease to neurologic diseases such as dementia and depression. Exciting recent research points to chronic inflammation as an underlying contributor to many age-related chronic diseases. Cross-sectional and longitudinal studies in animals and humans have shown both an acute and a chronic anti-inflammatory effect. Because innate immunity is a key regulator of inflammatory processes, and chronic inflammation contributes to many illnesses, the effect of regular exercise on innate immunity, most importantly macrophages, holds much promise in terms of defining these mechanisms. Unfortunately, the mechanisms responsible for the observed anti-inflammatory effect of regular exercise have not been elucidated. This article presents several compelling potential mechanisms for the anti-inflammatory effect of exercise, including loss of body fat, reductions in macrophage accumulation in adipose tissue, altered macrophage phenotype in adipose tissue, exercise-induced muscle production of IL-6, or alterations in the balance between the sympathetic and parasympathetic nervous systems. Further investigation to confirm or reject these testable hypotheses will allow better application of exercise therapy to treat and prevent illnesses associated with chronic inflammation.

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... Long-term infections and autoimmune diseases are not unrelated to each other. In consequence of investigations, it was determined that inflammation is connected with a lot of chronic diseases, like ischemic cardiovascular diseases, stroke, chronic obstructive pulmonary disease, Alzheimer's disease, and type 2 diabetes mellitus (Woods, Vieira, and Keylock 2009). ...
... Exercise diminishes inflammation, which is brought on by chronic illnesses, according to both epidemiological and long-term study. Furthermore, it is claimed that exercise, both short-term and long-term, affects inflammation (Metsios, Moe, and Kitas 2020;Woods et al. 2009). For these reasons, the effects of both acute and chronic exercise on inflammation are examined in this chapter using the most current information. ...
... However, if there is a lack of resting time and/or conditions in which the body is overloaded, the damage could become chronic. Thus, chronic inflammation could be result with overloaded exercise syndrome which characterized by fatigue, depression, paint in the joint and loss of appetite (He et al. 2016;Woods et al. 2009). Based on these, when it is indicated that chronic exercise has anti-inflammatory effects, acute exercise is usually related to inflammation (Woods et al. 2009). ...
... Long-term infections and autoimmune diseases are not unrelated to each other. In consequence of investigations, it was determined that inflammation is connected with a lot of chronic diseases, like ischemic cardiovascular diseases, stroke, chronic obstructive pulmonary disease, Alzheimer's disease, and type 2 diabetes mellitus (Woods, Vieira, and Keylock 2009). ...
... Exercise diminishes inflammation, which is brought on by chronic illnesses, according to both epidemiological and long-term study. Furthermore, it is claimed that exercise, both short-term and long-term, affects inflammation (Metsios, Moe, and Kitas 2020;Woods et al. 2009). For these reasons, the effects of both acute and chronic exercise on inflammation are examined in this chapter using the most current information. ...
... However, if there is a lack of resting time and/or conditions in which the body is overloaded, the damage could become chronic. Thus, chronic inflammation could be result with overloaded exercise syndrome which characterized by fatigue, depression, paint in the joint and loss of appetite (He et al. 2016;Woods et al. 2009). Based on these, when it is indicated that chronic exercise has anti-inflammatory effects, acute exercise is usually related to inflammation (Woods et al. 2009). ...
... Many triggering factors, such as a fat-enriched diet and a high plasma leptin concentration, have been shown to affect T cell function and activate macrophages present in adipose tissue (16,20). In addition, factors such as monocyte chemoattractant protein that released from adipose tissue may activate macrophages (21). In addition, it has been shown that preadipocytes gain macrophage-like activity, and all these events cause cytokine responses (16,18). ...
... Apart from during resting conditions, it is noteworthy to mention that post-exercise cytokine responses show considerable variation. For example, in some studies where blood was collected just after the exercise, the IL-6 levels showed an increasing trend (24), whereas some studies claim that the immune response might have been suppressed due to glucocorticoids triggered by acute exercise stress, which in turn led to a decrease in cytokine release (21). In our study, the pre-training and posttraining IL-6 levels were not significantly ...
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Objective: This study's objective was to evaluate interleukin-6 (IL-6) and C-reactive protein (CRP) responses and performance changes in obese women after 8 weeks of aerobic training with an intensity of 50 to 60% of their individual maximum oxygen uptake (VO2). Methods: A total of 18 sedentary women with an average age of 44.3 (± 1.9) years volunteered for this study. Over a period of 8 weeks, in 4 40-minute sessions per week, the participants walked at an exercise intensity that caused their heart rates to increase to levels corresponding to 50 to 60% of their VO2 peaks. Blood samples were collected from the participants, both when they were at rest and a couple of minutes after the end of the 1st exercise session. Sampling was repeated in the 4th and 8th weeks, before and after the last training sessions. Results: The participants' body mass indices and weights decreased significantly by the end of the 8th week, while their maximum running speeds and VO2 peaks increased significantly. There were no differences in CRP or IL- 6 concentrations between the pre- and post-training sessions, but most of the participants' IL-6 levels dropped below 10 pg/ml after 8 weeks of training. Conclusion: Although no significant changes were observed in CRP or IL-6 concentrations, it is important to note that in response to aerobic training, the IL-6 levels of most of the participants fell to what is generally considered acceptable.
... Several studies reported an inverse relationship between circulating inflammatory adipokine levels and long-term physical activity [29,30]. Long-term physical activity combats metabolic syndrome by regulating TNF-α-induced insulin resistance [30,31]. Acute physical activity increases blood TNF-α concentrations by increasing circulatory TNF-α expression by immune cells. ...
... Thus, while acute physical activity transiently increases the levels of inflammatory cytokines, long-term physical activity especially aerobic exercise reduces circulating levels of inflammatory markers [75]. Thus, physical activity provides protective effects against the metabolic syndrome by regulating the release and activity of TNF-α and IL-6 and by attenuating TNF-α-induced insulin resistance [30,31]. ...
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We review the effects of acute and long-term physical activity on adipokine levels in individuals with type 2 diabetes (T2D). Three electronic databases were searched. Studies made in animal models were excluded, while studies based on participants with and without T2D, and also studies with type 1 diabetes were included. Of the 2,450 citations, 63 trials, including randomised control trials, cross-sectional and longitudinal studies, met our inclusion criteria. Seventy and five percent of studies reported the effects of physical activity on tumor necrosis factor-alpha (TNFα), interleukin 6 (IL-6), adiponectin, visfatin, omentin-1, and leptin levels. There are no robust results due to variations in exercise modality, intensity, duration, and also differences in cohort characteristics in the literature. Only four studies described the effects of an acute session of physical activity on adipokine levels. Overall, physical activity improves diabetes status by regulating adipokine levels. However, long-term aerobic + resistance training combined with dietary modifications is likely to be a more effective strategy for improving adipokines profiles in patients with type 2 diabetes.
... Physical activity (PA) is a leading candidate to treat CIN non-pharmacologically [18][19][20][21][22][23], purportedly through inducing axonal regeneration [24], central plasticity [25], and other health benefits such as improved aerobic capacity [26] and reduced systemic inflammation [27]. However, more work is needed to motivate habitual participation and optimize neurorecovery potential. ...
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Background Breast cancer (BC) is among the most common forms of cancer experienced by women. Up to 80% of BC survivors treated with chemotherapy experience chemotherapy-induced neuropathy (CIN), which degrades motor control, sensory function, and quality of life. CIN symptoms include numbness, tingling, and/or burning sensations in the extremities; deficits in neuromotor control; and increased fall risk. Physical activity (PA) and music-based medicine (MBM) are promising avenues to address sensorimotor symptoms. Therefore, we propose that we can combine the effects of music- and PA-based medicine through neurologic dance training (NDT) through partnered Adapted Tango (NDT-Tango). We will assess the intervention effect of NDT-Tango v. home exercise (HEX) intervention on biomechanically-measured variables. We hypothesize that 8 weeks of NDT-Tango practice will improve the dynamics of posture and gait more than 8 weeks of HEX. Methods In a single-center, prospective, two-arm randomized controlled clinical trial, participants are randomly assigned (1:1 ratio) to the NDT-Tango experimental or the HEX active control intervention group. Primary endpoints are change from baseline to after intervention in posture and gait. Outcomes are collected at baseline, midpoint, post, 1-month follow-up, and 6-month follow-up. Secondary and tertiary outcomes include clinical and biomechanical tests of function and questionnaires used to compliment primary outcome measures. Linear mixed models will be used to model changes in postural, biomechanical, and PROs. The primary estimand will be the contrast representing the difference in mean change in outcome measure from baseline to week 8 between treatment groups. Discussion The scientific premise of this study is that NDT-Tango stands to achieve more gains than PA practice alone through combining PA with MBM and social engagement. Our findings may lead to a safe non-pharmacologic intervention that improves CIN-related deficits. Trial registration This trial was first posted on 11/09/21 at ClinicalTrials.gov under the identifier NCT05114005.
... Abd El-Kader and Al-Jiffri showed that TNF-α levels in plasma decreased significantly after three months of aerobic and resisted exercise training in obese postmenopausal women (Abd El-Kader and Al-Jiffri 2019). It seems that exercise training may improve inflammatory conditions through reduction of the percentage of body fat and accumulation of macrophages in adipose tissue (Woods et al. 2009). Since the rat's weights did not change in the current study, it seems that it could not improve inflammatory factor levels such as TNF-α. ...
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Estrogen deficiency intensifies sarcopenia by activation of inflammatory and oxidative pathways. Aerobic exercise training and antioxidant/inflammatory supplements might reverse such outcomes or decline the degenerative pathway. Thus, we investigated the impact of aerobic training and crocin (CRO) consumption on skeletal muscle MuRf-1 and plasma antioxidant and inflammatory statues in ovariectomized (OVX) rat models fed on a high-fat diet (HFD). 72 female Wistar rats (200 ± 20 gr) were randomly divided into 9 groups: (1) non-OVX + standard chow (nOVX + SC), (2) nOVX + HFD, (3) high-intensity continuous training (HICT) + OVX + HFD + CRO, (4) HICT + OVX + HFD, (5) moderate-intensity continuous training (MICT) + OVX + HFD + CRO, (6) MICT + OVX + HFD, (7) OVX + HFD + CRO, (8) OVX + SC, and (9) OVX + HFD. The OVX rats underwent surgery for menopause model induction. Immediately after the ovariectomy, rats were fed either by HFD or SC. Seven weeks later, exercise training (HICT/MICT; 8-week, 5-session, 12–30 m/min or 12–21 m/min) and CRO consumption (60 mg/kg) intervention per sessions were performed. The plasma levels of SOD, GSH, and TNF-α and muscle levels of MuRf-1 were assessed using the ELISA method. A two-tailed t-test and one-way ANOVA were applied for data analysis. There was not a significant difference in the protein levels of MuRF1 as the CRO caused an increase in the TNF-α levels as compared to the control. HICT significantly decreased SOD levels as compared to the control, CRO, and MICT. There was no significant difference in GSH levels between intervention arms. Exercise training and CRO supplementations did not make any significant changes in muscle mass regulation factors in the OVX rat model.
... Inflammatory cytokines affect a number of signals, which mediate an innate immune response and can aid dysregulation in many diseases, including cancer [69,70]. Common inflammatory cytokines include white blood cell-secreted ILs and macrophage-secreted TNFs, both of which have been closely correlated with cancer initiation and progression [71,72]; both ILs and TNFs can be blocked by H 2 gas [73]. ...
Article
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Age-related diseases represent the largest threat to public health. Aging is a degenerative, systemic, multifactorial and progressive process, coupled with progressive loss of function and eventually leading to high mortality rates. Excessive levels of both pro- and anti-oxidant species qualify as oxidative stress (OS) and result in damage to molecules and cells. OS plays a crucial role in the development of age-related diseases. In fact, damage due to oxidation depends strongly on the inherited or acquired defects of the redox-mediated enzymes. Molecular hydrogen (H2) has recently been reported to function as an anti-oxidant and anti-inflammatory agent for the treatment of several oxidative stress and aging-related diseases, including Alzheimer’s, Parkinson’s, cancer and osteoporosis. Additionally, H2 promotes healthy aging, increases the number of good germs in the intestine that produce more intestinal hydrogen and reduces oxidative stress through its anti-oxidant and anti-inflammatory activities. This review focuses on the therapeutic role of H2 in the treatment of neurological diseases. This review manuscript would be useful in knowing the role of H2 in the redox mechanisms for promoting healthful longevity.
... Under physiological conditions, PE induces several intracellular signaling pathways that result in cellular endurance and adaptation in the musculoskeletal system [26,27]. Moreover, PE also influences the regulation of innate immunity and inflammation [28,29]. ...
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Lifestyle modifications in preclinical Rheumatoid Arthritis (RA) could delay the ongoing pathogenic immune processes and potentially prevent its onset. Physical exercise (PE) benefits RA patients; however, its impact in reducing the risk of developing RA has scarcely been studied. The objective was to describe the effects of low-intensity PE applied at the disease’s preclinical phase on the joints of DBA/1 mice with collagen-induced arthritis (CIA). Twelve mice with CIA were randomly distributed into two groups: the CIA-Ex group, which undertook treadmill PE, and the CIA-NoEx, which was not exercised. The effects of PE were evaluated through clinical, histological, transcriptomics, and immunodetection analyses in the mice’s hind paws. The CIA-Ex group showed lower joint inflammation and damage and a decreased expression of RA-related genes (Tnf Il2, Il10, Il12a, IL23a, and Tgfb1) and signaling pathways (Cytokines, Chemokines, JAK-STAT, MAPK, NF-kappa B, TNF, and TGF-beta). TNF-α expression was decreased by PE in the inflamed joints. Low-intensity PE in pre-arthritic CIA reduced the severity through joint down-expression of proinflammatory genes and proteins. Knowledge on the underlying mechanisms of PE in preclinical arthritis and its impact on reducing the risk of developing RA is still needed.
... Both aerobic and muscle strength training stimulate the release of myokines (e.g., myostatin, IL-6, IL-15, and LIF) [757], which in the long term counteract low-grade chronic inflammation [758]. Exercising can also boost innate [759] and adaptive immune responses [760][761][762], and helps to maintain local tissue immunity [763] (e.g., in the lungs [756]) and to delay immunosenescence [764]. In addition to immunological functions, regular exercising helps to slow down the deterioration of frailty by preserving muscle [765] and respiratory function [766], and prevents body fat accumulation [767] and the development of CVD [768]. ...
Article
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The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease and death. Understanding the risk factors of severe COVID-19 is relevant both in the clinical setting and at the epidemiological level. Here, we provide an overview of host, viral and environmental factors that have been shown or (in some cases) hypothesized to be associated with severe clinical outcomes. The factors considered in detail include the age and frailty, genetic polymorphisms, biological sex (and pregnancy), co- and superinfections, non-communicable comorbidities, immunological history, microbiota, and lifestyle of the patient; viral genetic variation and infecting dose; socioeconomic factors; and air pollution. For each category, we compile (sometimes conflicting) evidence for the association of the factor with COVID-19 outcomes (including the strength of the effect) and outline possible action mechanisms. We also discuss the complex interactions between the various risk factors.
... But long term high impact exercise could literally lower the count of circulating leucocytes and will enhance the production of cortisol. [3] Exercise may increase natural killer cell count and cytolytic action [4] while decrease C reactive protein in blood. In individuals with heart problems it lowers blood fibrinogen levels [5] . ...
... However, molecular mechanisms underlying these effects are mainly obscure. Moreover, depending on the exercise protocols, interpersonal variations, and a number of lifestyle factors, the observed effects of exercise on human health have been different (Woods et al., 2006). Previous studies have reported the effect of exercise on regulation of expression of genes participating in inflammatory responses, cellular communication and signal transduction (reviewed in (Gjevestad et al., 2015)). ...
Article
Regular physical activity (exercise) has been shown to improve physical and mental health. The beneficial effects of exercise in prevention of metabolic abnormalities, diabetes mellitus, cardiovascular disorders and neoplastic conditions have been reported by several groups. However, the mechanisms underlying the beneficial effects of exercise are not fully clarified. Several studies have indicated changes in expression of genes following certain periods of regular physical activity. Genes regulating immune responses, metabolic pathways, neurogenesis, myelin repair, neurological function recovery and mitochondrial biogenesis/functions are among those being affected by exercise. Moreover, a number of microRNAs including miR-122, miR-192 and miR-22 are influenced by exercise. Besides, polymorphisms in a number of genes such as ACTN3, SNAP-25, IGF-1, AKT2, Myostatin and IL-6 can influence exercise-related phenotypes. In the current review, we provide a summary of studies which reported the effects of exercise on gene expression as well as the significance of genetic variations in determination of exercise-related phenotypes.
... Therefore, in the absence of an oxidative status, the self-renewal capacity of cells and autophagy processes are disrupted, with the accumulation of chromosomal defects and abnormalities and the inability to repair DNA and induce apoptosis [225,226]. Highly active antioxidant systems induce reductive stress, influencing [130] cell growth and mitochondrial functions and are incriminated in the progression of pathological conditions such as Alzheimer's disease [227] because of an impaired protein folding process [12], or cardiomyopathy, cancer, or metabolic syndrome [86,[228][229][230]. Some examples of the negative influence of the most frequently used antioxidant substances are illustrated in Table 1. ...
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Oxidative stress is the subject of numerous studies, most of them focusing on the negative effects exerted at both molecular and cellular levels, ignoring the possible benefits of free radicals. More and more people admit to having heard of the term “oxidative stress”, but few of them understand the meaning of it. We summarized and analyzed the published literature data in order to emphasize the importance and adaptation mechanisms of basal oxidative stress. This review aims to provide an overview of the mechanisms underlying the positive effects of oxidative stress, highlighting these effects, as well as the risks for the population consuming higher doses than the recommended daily intake of antioxidants. The biological dose–response curve in oxidative stress is unpredictable as reactive species are clearly responsible for cellular degradation, whereas antioxidant therapies can alleviate senescence by maintaining redox balance; nevertheless, excessive doses of the latter can modify the redox balance of the cell, leading to a negative outcome. It can be stated that the presence of oxidative status or oxidative stress is a physiological condition with well-defined roles, yet these have been insufficiently researched and explored. The involvement of reactive oxygen species in the pathophysiology of some associated diseases is well-known and the involvement of antioxidant therapies in the processes of senescence, apoptosis, autophagy, and the maintenance of cellular homeostasis cannot be denied. All data in this review support the idea that oxidative stress is an undesirable phenomenon in high and long-term concentrations, but regular exposure is consistent with the hormetic theory.
... Aerobics in diabetes has been suggested, the main of which is to reduce white adipose tissue mass and change the secretion of proinflammatory mediators, especially IL-6, adipokines, and TNF-α, as well as reduce the permeability of macrophages in the M1 family and increase the perme-ability of macrophages in the M2 family. The tissue is adipose (33,34). ...
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: Type 2 diabetes is one of the most important metabolic disorders that affect lifestyle. Accordingly, studies have shown that lifestyle changes, especially increasing daily physical activity, can prevent diabetes and help people with the disease through various mechanisms. On the other hand, the use of medicinal plants due to having various phytochemical compounds, each of which has healing properties, can be considered a helpful method in preventing and treating diabetes complications. One of the phytochemical compounds used as an effective substance in the treatment of diabetes is an alkaloid called Berberine. Berberine has been used in traditional medicine to lower blood glucose, and new studies in both in vivo and in vitro conditions have confirmed the diabetic effect of Berberine. Receiving increased energy metabolism, increased glucose and fatty acid uptake by peripheral tissues, improving lipid profile, reducing inflammatory mediators, increasing antioxidant capacity are common mechanisms that aerobic exercise and Berberine exert their beneficial effects in diabetes. In the present study, the effect of aerobic exercise, Berberine, and its combination on diabetes markers have been investigated considering the beneficial effects of aerobic exercise and Berberine in diabetes.
... The main result of this study was that the prevalence of self-reported asthma and allergic diseases was lower in athletes than in the control group. It should be taken into account that many differences such as genetic variability, geographical conditions, differences in exercise intensity and duration, and other lifestyles factors may have an effect on this (39) . Although intense regular training over long periods of time may contribute to the development of asthma and other respiratory allergies, regular aerobic training promotes health and may prevents allergic disease by decreasing the systemic inflammation. ...
Article
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Objective: The prevalence and the risk factors influencing allergic disorders in amateur athletes are still poorly defined. The aim of this study was to evaluate the prevalence and risk factors of the common allergic disorders in school aged athletes compared with the general population in southwest of Turkey. Methods: Using the “International Study of Asthma and Allergy in Childhood (ISAAC) Phase I” questionnaire, 714 athletes aged 7-18 and 325 age-matched healthy controls were examined. Risk factors that would affect the prevalence were evaluated with the questions given in addition to this questionnaire. Results: In the athlete group, the prevalence of existing asthma, allergic rhinitis, and eczema was lower than controls [(3.8%) and (16.3%), respectively, p<0.001], [(18.7%) and (42.1%)], respectively, p <0.001] and [(5.5%) and (10.5%), respectively, p<0.001]. Multivariate logistic regression analysis revealed that in the athlete population, a previously known allergy increased risk of curent wheezing (odds ratio [OR] =5.3; confidence interval, [CI]=1.8-15.4), current allergic rhinitis ([OR]=2.8; [CI]=1.3-6.2), and current eczema [OR]=4.5; [CI]=1.1-17.1). Familial atopy increased risk of current allergic rhinitis (OR=2.2; CI=0.9-4.9), and current eczema ([OR] = 6.6; [CI]=1.7-25.7). Conclusion: This study is the first prevalence study using the ISAAC method in school-age sports children in southwestern Turkey. Unlike adults, the prevalence of asthma, allergic rhinitis and eczema was found to be lower than controls of the same age. It is thought that sports and spending more time outdoors in children reduce allergic inflammation.
... Physiotherapy is the tool to initiate the patient to return to life by exercising protocols. The type of training has various changes on the immunity, such as mostly followed training is the aerobic training as this creates body rush to remove toxins, suppress the effects of tumor treatment and cell growth and effects of inflammation caused by the tumor, as these all factors are immunity suppression factors [17]. Physiotherapy helps in healing of the patient in all means of the physical, psychological and physiological means. ...
Article
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Cancer is the disease with prolonged inflammation harming the immunity due to long term treatment. The immunity is the primary measure to prevent someone from the infection and upcoming inflammation. There are various methods followed nowadays to challenge the inflammation and boost immunity and overcome with the life measures towards affected immunity. The objective towards the study was to review literature and associate the relation between immunity boosters and Physiotherapy and their approach towards cancer in measure to enhance immunity. The relation between immunity boosters to immunity was associated with increase in immune response physiologically and an initiative towards the oncology rehabilitation. Moreover, physiotherapy relation came to be positive in increase in immunity with enhancement of all immune response with different exercise regimes initiating the better quality of life. Both the authors went through discussion process with the help of the literature review it came to the conclusion of the positive association between immunity boosters and Physiotherapy having a positive impact on the cancer to improve not only lifestyle but the immunity as an essential measure.
... While weight loss is associated with a substantial decrease in the risk of obesity-related diseases such as NAFLD, exercise seems to provide a wide range of health effects beyond weight loss [31]. Although it is generally accepted that a single bout of prolonged exercise can depress immunity, regular exercise can be beneficial for the host partly due to ameliorated inflammation [32]. Our data show that MIT and HIIT regimens decreased fat mass but also led to a slight decrease in total lean mass. ...
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Objective Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology ranging from simple fatty liver to non-alcoholic steatohepatitis (NASH). Notably, immune cell-driven inflammation is a key mechanism in the transition from fatty liver to the more serious NASH. Although exercise training is effective at ameliorating obesity-related diseases, the underlying mechanisms of the beneficial effects of exercise remain unclear. Whether there is an optimal modality and intensity of exercise to treat NAFLD is unknown. The objective of this study was to determine whether high-intensity interval training (HIIT) or moderate-intensity continuous training (MIT) is more effective at ameliorating the progression of NASH. Methods Wildtype mice were fed a high-fat high-carbohydrate (HFHC) diet for 6 weeks and left sedentary (SED) or assigned to either an MIT or HIIT regimen using treadmill running for an additional 16 weeks. MIT and HIIT groups were pair-fed to ensure energy intake was similar between the exercise cohorts. To determine changes in whole-body metabolism, we performed insulin and glucose tolerance tests, indirect calorimetry, and magnetic resonance imaging. NASH progression was determined by triglyceride accumulation, expression of inflammatory genes, and histological assessment of fibrosis. Immune cell populations in the liver were characterized by cytometry by time-of-flight mass spectrometry and progenitor populations within the bone marrow were assessed by flow cytometry. Finally, we analyzed the transcriptional profile of the liver by bulk RNA sequencing. Results Compared with SED mice, both HIIT and MIT suppressed weight gain, improved whole-body metabolic parameters, and ameliorated the progression of NASH by reducing hepatic triglyceride levels, inflammation, and fibrosis. However, HIIT was superior to MIT at reducing adiposity, improving whole-body glucose tolerance, and ameliorating liver steatosis, inflammation, and fibrosis, without any changes in body weight. Improved NASH progression in HIIT mice was accompanied by a substantial decrease in the frequency of pro-inflammatory infiltrating monocyte-derived macrophages in the liver and reduced myeloid progenitor populations in the bone marrow. Notably, an acute bout of MIT or HIIT exercise had no effect on the intrahepatic and splenic immune cell populations. In addition, bulk mRNA sequencing of whole liver tissue showed a pattern of gene expression confirming that HIIT was more effective than MIT in improving liver inflammation and lipid biosynthesis. Conclusions Our data suggest that exercise lessens hepatic inflammation during NASH by reducing the accumulation of hepatic monocyte-derived inflammatory macrophages and bone marrow precursor cells. Our findings also indicate that HIIT is superior to MIT in ameliorating the disease in a dietary mouse model of NASH.
... 6 Inflammation is two-to four-fold increments in circulating levels of pro-inflammatory cytokines and acute-phase proteins as well as minor increments in counts of leucocytes. 7 Both oxidative stress and inflammation appear to be involved in the pathogenesis of chronic diseases. Indeed, they seem to be the foundation of the most prevalent illnesses including cancers, cardiovascular diseases, metabolic disorders, diabetic complications, pain disorders, inflammatory diseases, neurological disorders and mental health illnesses. ...
Article
Background: Grape seed extract (GSE) seems to have antioxidant and anti-inflammatory properties due to its high polyphenolic content. Nevertheless, the scientific literature in this field is controversial and inconclusive. Therefore, we aimed to conduct a systematic review and meta-analysis of controlled trials to evaluate the effect of supplementation with GSE on biomarkers of oxidative stress and inflammation. Methods: Medline, Scopus, Cochrane Library, Google Scholar and Web of Science databases were searched up to 10 September 2020 using appropriate keywords without restrictions. In the systematic review phase, all biomarkers of oxidative stress and inflammation were considered as outcomes. In the meta-analysis phase, six biomarkers were selected as outcomes, and weighted mean difference (WMD) or standardised mean difference (SMD) with 95% confidence interval (CI) was calculated for them using a random-effects model. Results: Twenty-three studies were included in the systematic review, and 19 studies were included in the meta-analysis. GSE supplementation caused a significant decrease in malondialdehyde (SMD: −1.04, 95% CI: −1.65, −0.42), oxidised low-density lipoprotein (SMD: −0.44, 95% CI: −0.75, −0.13) and high-sensitivity C-reactive protein (WMD: −0.48 mg/L, 95% CI: −0.94, −0.03) and a marginally significant increase in total antioxidant capacity (SMD: 0.49, 95% CI: −0.05, 1.04) but did not significantly influence C-reactive protein (WMD: −0.36 mg/L, 95% CI: −1.02, 0.30) and white blood cell count (WMD: 0.12 × 109/L, 95% CI: −0.25, 0.48). Conclusion: It appears that GSE supplementation can remarkably modulate the body's redox system, particularly through the inhibition of lipid peroxidation, but has neutral or mildly beneficial effects on inflammatory responses.
... A clinical study in twenty-one participants by Passos et al. summarized that longterm moderate aerobic exercise training improved sleep, lowered depression and cortisol, and enhanced significant changes in immunologic variables like increased plasma apolipoprotein A and decreased CD4 and CD8 [36]. In another study, Woods et al. summed up that routine exercise protects against neural diseases such as dementia and depression through potential pathways including weight loss, declines in macrophage accumulation in adipose tissue, macrophage modifications, exercise-induced muscle development of IL-6, for the effect of antiinflammatory activities [37]. Exercise is compared to antidepressant medication as a first-line treatment for mild to moderate depression. ...
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In the 21st century, any pandemic, especially, SARS-CoV-2 is a global burden due to high incidence, mortality, and mutation rate. Although several techniques have already been identified to control the pandemic or treat patients and causes of adverse impact on mental health, relatively only, fewer researchers have little concern about finding effective mitigation strategies to improve mental health. Therefore, this study aimed to find some common and unique approaches to manage mental health during a pandemic. Some strategies for the better management of mental health induced by SARS-CoV-2 infections are required for all classes of peoples. Early management is vital, and those must be associated with frontline workers and people staying at home, particularly in isolation centers and already identified as active cases. Experts have pointed out the need to pay specific attention to proper daily life. To manage abnormal mental conditions, such as anxiety, mood, personality, and psychotic disorder during the pandemic; social media, meditation, and psychological motivation with adequate diet, exercise, and sleep have significant roles in regulating some biological mechanism, incredibly immune, hormonal, and neural process. Management of mental health is mandatory for all at the time of the SARS-CoV-2 pandemic. We can consider all of the strategies mentioned above to treat mental health during and after the COVID- 19 pandemic condition.
... In fact, physical activity was shown to induce cellular and molecular changes in the adipose tissue in a way that alleviates the lowgrade chronic inflammation that accompanies obesity (8)(9)(10)(119)(120)(121). The underlying mechanisms that contribute to the exercise-induced anti-inflammatory responses have not been completely elucidated. A major contributor to the reduction in inflammation accompanying exercise may reside in the mediation of ATM (14,113,116,122,123). ...
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With increasing adiposity in obesity, adipose tissue macrophages contribute to adipose tissue malfunction and increased circulating proinflammatory cytokines. The chronic low-grade inflammation that occurs in obesity ultimately gives rise to a state of metainflammation that increases the risk of metabolic disease. To date, only lifestyle and surgical interventions have been shown to be somewhat effective at reversing the negative consequences of obesity and restoring adipose tissue homeostasis. Exercise, dietary interventions, and bariatric surgery result in immunomodulation, and for some individuals their effects are significant with or without weight loss. Robust evidence suggests that these interventions reduce chronic inflammation, in part, by affecting macrophage infiltration and promoting a phenotypic switch from the M1- to M2-like macrophages. The purpose of this review is to discuss the impact of dietary fatty acids, exercise, and bariatric surgery on cellular characteristics affecting adipose tissue macrophage presence and phenotypes in obesity.
... First, before talking about potential immunomodulatory agents, we have to mention that pharmacological interventions [58]. Immuno-modulators have the potential to inhibit cytokines and treat the cytokine storm. ...
Article
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the novel coronavirus disease 2019 (COVID-19). The principal risk factor for the development of serious forms of COVID-19 was found to be the precarious metabolic health. There are several mechanisms that are implicated in the seriousness of COVID-19 ranging from attenuation of immune system function to chronic inflammation. It is important to keep in mind that obesity is a complex disease when discussing the relation between obesity and the severity of COVID-19. An increasing body of proof links obesity to COVID-19. Obesity has an obvious role in the high incidence, symptoms severity and mortality rates of viral infections seen in obese patients. Adipose tissue shows a high expression of the angiotensin-converting enzyme 2 (ACE2), the receptor for entry of SARS-CoV-2 into host cells, so obese population exhibit higher vulnerability to COVID-19. The primary immune response is offered mainly by type-I interferon (IFN-I) that is suppressed in COVID-19. The pro-inflammatory state associated with obesity produces imbalance of the inflammatory response to COVID-19, as the cytokine storm found in subjects with serious disease form. Obesity is considered as chronic inflammation of low degree, so it shows a capacity for pathogenic immune amplification. In this review, the effect of obesity on the immune system is described. The authors described the dysfunctional immune responses caused by obesity that lead to organ injury in COVID-19 infection and impair the ability of patient to combat the virus. Further research is required to assess the impact of obesity control, immunonutrition and physical exercise in SARS-CoV-2 infection.
... 49 Evidence suggests that regularly performed LTPA, moderate to vigorous may reduce markers of systemic inflammation. 50 However, there is a substantial body of evidence that high-intensity or prolonged endurance training leads to increased oxidative stress that may result in a pro-inflammatory response from the immune system to protect the host tissue. 51 In addition, an increase in the expression of pro-inflammatory cytokines can be crucial for long-term adaptive responses to exercise training. ...
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Background Scientific evidence has shown that an increase in regular physical activity is associated with a decrease in the development of many types of cancer. Potential mechanisms that link physical activity to reduced cancer risk include a decrease in systemic inflammation, hyperinsulinemia, insulin-like growth factor (IGF-I), sex hormones, pro-inflammatory leptin and other obesity-related cytokines, and a significant increase in anti-inflammatory adiponectin levels. In addition, physical activity improves immune function and the composition and diversity of the gastrointestinal microbiota. Moderate physical activity is important for cancer protection, but the most significant changes in the inflammatory profile are conferred by physical activity performed at higher intensities. Thus, there is a need for further investigation into the type, intensity, and duration of physical activity for the prevention of some types of cancer and the development of effective recommendations. Conclusions There is a strong evidence that physical activity of moderate to vigorous intensity protects against colon and breast cancer, and probably against cancer at all other sites.
... Acute physical exercise, when performed, can generate several transient changes in the body. Besides, physiological adaptations are also developed in response to stress to reestablish homeostasis, greatly influencing the immune response [8][9][10]. Throughout the athleteʼs life, immune cells undoubtedly suffer from metabolism transformation when adapting to periods of energy overload and physiological stress, thus creating a metabolic landscape that, in turn, improves immunosurveillance and viral response. ...
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The world is experiencing a severe new pandemic, in which the elderly afflicted with chronic diseases are the most affected. The aging of the immune system (immunosenescence) reduces its efficacy against viral infections and increases its susceptibility to repeated acute infections, such as the flu. The improvement of the immune system functioning leading to a reduced incidence of infections can be achieved with regular physical exercise, besides its countless other benefits. The immunosenescence delay in master athletes, protecting them from possible viral infections, has been recently shown. Here the role of aerobic exercise training as an immune system fine-tuning regulator was discussed, focusing on lifelong athletes and specifically on the age-impaired antibody production in immunized elderly and the effects of lifelong physical exercise on the anti-inflammatory and vaccine response optimization. Moreover, the aerobic training effects on the natural killer (NK) cell activity and the underlying mechanisms responsible for a better antiviral response in active elderly and/or master athletes were addressed. It was hypothesized that lifelong exercise training delays age-related decrements in immunity by remodeling the metabolism of different cells (e.g., NK cells), creating a metabolic scenario that in turn improves the immune systemʼs viral response. Lifelong exercisers present a preserved immune response to exercise, indicating that they are better prepared to respond to new immune challenges. Thus, master athletes and lifelong exercisers are possibly protected against or could mitigate the COVID-19 disease.
... Exercise is considered to be a method in controlling the expression of inflammation markers (Neves Miranda et al., 2015) and coagulation markers (Kupchak et al., 2017). Exercise has an effect on anti-inflammatory, including reduced IL-6 and TNF-a (Woods et al., 2009). Exercise also has effects on coagulation and fibrinolysis, which could significant degrade fibrinogen (El-Sayed et al., 2004). ...
Article
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Inflammation and the coagulation cascade are considered to be the potential mechanisms of ambient particulate matter (PM) exposure-induced adverse cardiovascular events. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and fibrinogen are arguably the four most commonly assayed markers to reflect the relationships of PM with inflammation and blood coagulation. This review summarized and quantitatively analyzed the existing studies reporting short- and long-term associations of PM2.5(PM with an aerodynamic diameter ≤2.5 μm)/PM10 (PM with an aerodynamic diameter≤10 μm) with important inflammation and blood coagulation markers (TNF-α, IL-6, IL-8, fibrinogen). We reviewed relevant studies published up to July 2020, using three English databases (PubMed, Web of Science, Embase) and two Chinese databases (Wang-Fang, China National Knowledge Infrastructure). The OHAT tool, with some modification, was applied to evaluate risk of bias. Meta-analyses were conducted with random-effects models for calculating the pooled estimate of markers. To assess the potential effect modifiers and the source of heterogeneity, we conducted subgroup analyses and meta-regression analyses where appropriate. The assessment and correction of publication bias were based on Begg’s and Egger’s test and “trim-and-fill” analysis. We identified 44 eligible studies. For short-term PM exposure, the percent change of a 10 μg/m³ PM2.5 increase on TNF-α and fibrinogen was 3.51% (95% confidence interval (CI): 1.21%, 5.81%) and 0.54% (95% confidence interval (CI): 0.21%, 0.86%) respectively. We also found a significant short-term association between PM10 and fibrinogen (percent change = 0.17%, 95% CI: 0.04%, 0.29%). Overall analysis showed that long-term associations of fibrinogen with PM2.5 and PM10 were not significant. Subgroup analysis showed that long-term associations of fibrinogen with PM2.5 and PM10 were significant only found in studies conducted in Asia. Our findings support significant short-term associations of PM with TNF-α and fibrinogen. Future epidemiological studies should address the role long-term PM exposure plays in inflammation and blood coagulation markers level change.
... Chronic inflammation is independently associated with the incidence and progression of insulin resistance, atherosclerosis, neurodegeneration and tumour growth [1][2][3][4] . These pathophysiologies underlie the most pervasive chronic conditions of the developed world, including cardiovascular disease, cancer, diabetes, dementia and chronic obstructive pulmonary disease 5,6 . Therefore, targeting chronic inflammation to address pathophysiologies could be a promising strategy to prevent chronic disease. ...
Article
Objectives: Chronic inflammation is independently associated with the incidence and progression of chronic disease. Exercise has been found to reduce chronic inflammation, however the role of exercise intensity (work rate) is unknown. This review aimed to determine the pooled effect of higher- compared to lower-intensity aerobic and resistance exercise on chronic inflammation in adults. Design: Systematic review and meta-analysis. Methods: Five electronic databases were searched. Intervention trials that assessed the effect of ≥2 different exercise intensities on peripheral markers of chronic inflammation [c-reactive protein (CRP), interleukin (IL)-6, tumour necrosis factor (TNF)-α and IL-10] in adults were included. Random-effect meta-analyses were conducted to calculate the mean difference in change scores between groups [effect size (ES)]. Sub-group analyses were performed to explore the influence of age, chronic disease, body mass index and intervention duration on inflammation heterogeneity. Results: Of 3952 studies identified, 27 were included. There were no significant effects of exercise intensity on IL-6 (ES=-0.039, 95%CI=-0.353–0.275; p = 0.806), TNF-α (ES = 0.296, 95%CI=-0.184–0.777; p = 0.227) and IL-10 (ES = 0.007, 95%CI=-0.904–0.919; p = 0.987). A significant pooled ES was observed for higher- versus lower-intensity exercise on CRP concentrations, in studies of middle-aged adults (ES=-0.412, 95%CI=-0.821– -0.004, p = 0.048) or interventions >9 weeks in duration (ES=-0.520, 95%CI=-0.882–-0.159, p = 0.005). Conclusions: Exercise intensity did not influence chronic inflammatory response. However, sub-analyses suggest that higher-intensity training may be more efficacious than lower-intensity for middle-aged adults, or when longer duration interventions are implemented (>9 weeks), in the most commonly-reported analyte (CRP).
... Numerous authors agree in the effects of physical exercise on the AT [18][19][20][21], such as changes in the AT phenotype that lead to a significant decrease of M1 macrophages and an increase of M2 macrophages, as well as the secretion of more anti-inflammatory cytokines, such as IL-6 and TNF-α [22]. Other researchers have studied the possible changes in the signaling pathways after implementing exercise programs, reporting a decrease of postprandial lipemia, a reduction in NF-kB signaling, and an increase in AMPK signaling (showing anti-inflammatory properties) [23][24][25]. The interest of these studies is increasingly focused on determining the most adequate training to reduce the inflammatory state and its effects on metabolic syndrome in people with obesity. ...
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Obesity is related to low-grade systemic inflammation. This state of inflammation is characterized by the alteration in adipokine regulation, which may lead to a situation of cardiometabolic risk. The aim of this study was to evaluate the effects of a concurrent training program on markers of lipoinflammation in adult people with obesity, comparing the response to the training between men and women. A quasi-experimental, quantitative, and longitudinal study with a pre-post intervention was conducted. An 8-week concurrent training program was carried out, in which 26 individuals with obesity participated (mean ± SD; age = 46.38 ± 4.66) (BMI = 36.05 ± 4.99) (12 men and 14 women). Before and after the intervention period, blood samples were taken by percutaneous puncture. The blood levels of adiponectin and leptin were evaluated. Significant differences were obtained in the adiponectin-leptin ratio (A/L ratio) of the entire sample (p = 0.009, ES = 0.53), which indicates a decrease in the risk of cardiovascular diseases and lipoinflammation. There were no significant differences in the improvements observed after the training in A/L ratio between women (A/L change = +63.5%) and men (A/L change= +59.2%). It can be concluded that the combination of aerobic exercise and resistance training induced an improvement in markers of lipoinflammation and cardiometabolic risk in the individuals with obesity evaluated in this study.
... Four inflammatory markers will be assessed using blood samples at baseline and month 6, as they are associated with PC patients' mortality [39,40]: C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin 4 (IL-4). CRP is selected because it is a global marker of inflammation and is predictive of chronic conditions, including cardiovascular disease [41]. TNF-alpha similarly indicates a systemic inflammatory state. ...
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Background: Prostate cancer is the most commonly diagnosed cancer in both African American and Hispanic men. Active surveillance is a treatment option for low- or very low-risk prostate cancer survivors, and lifestyle interventions have been found to reduce the disease progression and improve the quality of life for both survivors and their partners. To date, no lifestyle interventions that specifically target African American or Hispanic men and their partners exist. This protocol describes a study that tests the feasibility of a randomized controlled trial, a lifestyle intervention developed to enhance healthy lifestyle and quality of life among African American and Hispanic men on active surveillance and their partners. Methods: A mixed-method study, including a two-arm randomized controlled trial (n = 30 dyads in the intervention arm and n = 10 dyads in the control arm) and in-depth interviews, will be conducted. Intervention arm participants will receive bi-weekly health coaching calls (a total of 12 calls based on Motivational Interviewing), as well as physical activity-specific (e.g., power point slides, print materials about physical activity, and activity trackers for self-monitoring) and nutrition-specific education (e.g., two nutrition counseling sessions from a registered dietitian, print materials about nutrition, and food intake recording for self-monitoring) over 6 months. All participants will be assessed at baseline, month 3, and month 6. Blood will be collected at baseline and month 6 from the prostate cancer survivors. Finally, in-depth interviews will be conducted with subsamples (up to n = 15 dyads in the intervention arm and up to n = 5 dyads in the control arm) at baseline and months 3 and 6 to conduct a process evaluation and further refine the intervention. Discussion: If effective, the intervention may have a higher health impact compared with a typical lifestyle intervention targeting only survivors (or partners), as it improves both survivors' (tertiary prevention) and partners' health (primary prevention). Results from this study will provide important information regarding recruiting racial/ethnic minority cancer survivors and their partners. Lessons learned from this study will be used to apply for a large-scale grant to test the impact of the dyadic intervention in a fully powered sample. Trial registration: ClinicalTrials.gov (NCT No. 03575832) registered on 3 July 2018.
... Th e overall eff ect is a more anti-infl ammatory status which comprehensively improves endoneurial oxygen tension in the sural nerves, reduces oxidative stress, and decreases neurotrophic factors. All the metabolic, cardiopulmonary, and infl ammatory changes exert combined and PE dose-related eff ects to maintain healthy peripheral nerves function & associated vascular structure and ultimately improve overall DPN [96,97]. ...
Article
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Diabetes mellitus is the leading etiology for Diabetic Peripheral Neuropathy (DPN). There is no definitive treatment for it. Evidence progressively indicates the decisive role of regular Physical Exercise (PE) on enhancing DPN from clinical perspectives. However, there is a literature agreement on the consequence of PE on diabetes. But the evidence is still scattered and in need of further appraisal about exercise and DPN. This review aims to address the DPN burden comprehensively from an epidemiological angel, clinical presentation & diagnosis, and management. Further, it explores the effect of regular PE on DPN on attempts to answer the reasons behind PE induce an effect on diabetic peripheral neuropathy.
... 15,[57][58][59][60]64 Although acute episodes of exercise increase the level of inflammatory cytokines (Figure 3), chronic endurance exercise reduces the circulating levels of inflammatory markers that are usually higher in individuals with obesity ( Figure 4). [55][56][57][58]64 PA-mediated protective effects during the metabolic syndrome are exerted by controlling the release and activity of TNF-α and IL-6, reducing TNF-α-induced insulin resistance 65,66 and lowering CRP, IL-6 and TNF-α levels while increasing levels of antiinflammatory modulators such as IL-4 and IL-10. [67][68][69] The studies investigating the effects of acute exercise on TNF-α levels in individuals with obesity (Table 1) reported either an increase 70,71 or no change 72,73 in plasma levels following exercise. ...
Article
This narrative review summarizes current knowledge on the effects of physical activity (PA) on adipokine levels in individuals with overweight and obesity. Approximately 90 investigations including randomized control, cross‐sectional and longitudinal studies that reported on the effects of a single session of PA (acute) or long‐term PA (chronic) on adipokine levels in individuals with overweight/obesity were reviewed. The findings support the notion that there is consensus on the benefits of chronic exercise training—regardless of the mode (resistance vs. aerobic), intensity and cohort (healthy vs. diabetes)—on adipokine levels (such as tumour necrosis factor‐alpha, interleukin‐6, adiponectin, visfatin, omentin‐1 and leptin). However, several confounding factors (frequency, intensity, time and type of exercise) can alter the magnitude of the effects of an acute exercise session. Available evidence suggests that PA, as a part of routine lifestyle behaviour, improves obesity complications by modulating adipokine levels. However, additional research is needed to help identify the most effective interventions to elicit the most beneficial changes in adipokine levels in individuals with overweight/obesity.
... Exercise is considered to be a method in controlling the expression of inflammation markers (Neves Miranda et al., 2015) and coagulation markers (Kupchak et al., 2017). Exercise has an effect on anti-inflammatory, including reduced IL-6 and TNF-a (Woods et al., 2009). Exercise also has effects on coagulation and fibrinolysis, which could significant degrade fibrinogen (El-Sayed et al., 2004). ...
Article
Full-text available
Several epidemiological studies have evaluated the fractional exhaled nitric oxide (FeNO) of ambient air pollution but the results were controversial. We therefore conducted a systematic review and meta-analysis to investigate the associations between short-term exposure to air pollutants and FeNO level. We searched PubMed and Web of Science and included a total of 27 articles which focused on associations between ambient air pollutants (PM10, PM2.5, black carbon (BC), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3)) exposure and the change of FeNO. Random effect model was used to calculate the percent change of FeNO in association with a 10 or 1 μg/m³ increase in air pollutants exposure concentrations. A 10 μg/m³ increase in short-term PM10, PM2.5, NO2, and SO2 exposure was associated with a 3.20% (95% confidence interval (95%CI): 1.11%, 5.29%), 2.25% (95%CI: 1.51%, 2.99%),4.90% (95%CI: 1.98%, 7.81%), and 8.28% (95%CI: 3.61%, 12.59%) change in FeNO, respectively. A 1 μg/m³ increase in short-term exposure to BC was associated with 3.42% (95%CI: 1.34%, 5.50%) change in FeNO. The association between short-term exposure to O3 and FeNO level was insignificant (P>0.05). Future studies are warranted to investigate the effect of multiple pollutants, different sources and composition of air pollutants on airway inflammation.
... One of the promising pathways that underlie this association is inflammation, a known hallmark of cancer [94]. Furthermore, diet and physical activity may reduce systemic inflammation [95,96]. ...
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Evidence has emerged implicating epigenetic alterations in inflammatory breast cancer (IBC) origin and progression. IBC is a rare and rapidly progressing disease, considered the most aggressive type of breast cancer (BC). At clinical presentation, IBC is characterized by diffuse erythema, skin ridging, dermal lymphatic invasion, and peau d’orange aspect. The widespread distribution of the tumor as emboli throughout the breast and intra- and intertumor heterogeneity is associated with its poor prognosis. In this review, we highlighted studies documenting the essential roles of epigenetic mechanisms in remodeling chromatin and modulating gene expression during mammary gland differentiation and the development of IBC. Compiling evidence has emerged implicating epigenetic changes as a common denominator linking the main risk factors (socioeconomic status, environmental exposure to endocrine disruptors, racial disparities, and obesity) with IBC development. DNA methylation changes and their impact on the diagnosis, prognosis, and treatment of IBC are also described. Recent studies are focusing on the use of histone deacetylase inhibitors as promising epigenetic drugs for treating IBC. All efforts must be undertaken to unravel the epigenetic marks that drive this disease and how this knowledge could impact strategies to reduce the risk of IBC development and progression.
... Zielinski et al. attributed the decrease and delay of tumor growth in the experimental group to the control group after 4 weeks of endurance training to a decrease in the amount of immune cells in the tumor (27). According to Murphy et al.'s research, aerobic activity decreased tumor growth in the training group compared to the control group (28); however, some studies have shown no effect of exercise on tumor volume changes (29,30). The training protocol of the present study is defined on the treadmill; therefore, differences in training style, training duration, and type of induced tumor may be the reason for the results inconsistent with the results of the present study. ...
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BACKGROUND AND OBJECTIVE: Many deaths from cancer are due to metastases, a process which involves the epithelial-mesenchymal transition (EMT). On the other hand, regular exercise plays an important role in inhibiting the progression of breast cancer. Therefore, the purpose of this study was to investigate the influence aerobic interval training on expression of mesenchymal biomarkers, and tumor volume in mice with breast cancer. METHODS: In this experimental study, Thirty-two female BALB/c mice, aged 3-5 weeks (17±1g) were used. The mice were allocated to four groups: Exercise Tumor, Exercise (aerobic Interval training was performed six weeks (40 minutes) before and four weeks (30 minutes) after the induction of carcinoma with active recovery), Rest Tumor, Rest (Control- without exercise), Rest, Tumor, Exercise, (four weeks after the induction of carcinoma) and Exercise, Tumor, Rest (six weeks before the induction of carcinoma). The real-time PCR method was used to evaluate the expression of Vimentin and Twist. FINDINGS: The results of present study demonstrated that tumor tissue Vimentin expression in the Exercise Tumor Exercise (223.0±0.073) group decreased significantly (p= 0.0001), Also, the expression of Twist gene was significantly reduced in Exercise Tumor Exercise group (0.24±0.227) compared to control group (p=0.008). A significant decrease in tumor volume was observed in both RTE and ETE groups compared to the control group (RTR) (p = 0.0001). CONCLUSION: Based on the results of this study, a period of interval aerobic training can decrease the expression of Vimentin، Twist and decrease the tumor volume ratio.
... The inflammatory response that can occur as a result of exercise is complex and may occur as a result of increased reactive oxygen species. While some exercise can reduce acute or chronic inflammation (Woods et al. 2009), exercise can also induce inflammation in the aforementioned scenarios of muscle damage including eccentric, prolonged, and intense exercise (Byrne et al. 2004). Following exercise of this type, muscle damage incites the inflammatory response (Miles et al. 2008). ...
Article
Intense exercise, especially involving eccentric contractions, causes muscle damage concomitant with increased reactive oxygen species (ROS), which can lead to increased fatigue and decrements in physical performance. Additionally, inflammatory cytokines and advanced glycation end-products (AGEs) are produced as a result of eccentric exercise and may further lead to decreased exercise performance. Nutritional interventions may provide an avenue to respond to and reduce the symptoms associated with muscle damage. Of recent interest, curcumin, the main constituent in the spice turmeric, has been the focus of various studies considering post-exercise recovery. Curcumin has potent anti-oxidant and anti-inflammatory properties and can reduce the accumulation of AGEs. This review considers the current evidence for curcumin to impact muscle recovery following exercise to improve performance and the potential mechanisms of action. To date, clinical studies have considered the potential role of curcumin to reduce muscular damage following treadmill running (downhill and flat), conventional walking/running, cycling (acute and chronic), single-leg jumping (downhill), and eccentric muscular fitness exercises of the upper and lower body (single- and double-leg). Studies have been conducted in sedentary to highly active men and women, both young and old, with supplementation duration lasting from a single, acute dose to daily dosages for three months. Various curcumin-based interventions have improved self-perceived measures of pain and tenderness, reduced evidence of muscle damage, ameliorated inflammatory markers, increased markers of antioxidant capacity, diminished markers of oxidative stress, reduced markers of AGEs, and attenuated loss in mean power of single-leg sprints. However, these findings have not been consistently reported.
... Physical activity has also been associated with improvements in the immune response with increased surveillance and elimination of cancerous cells 33,34 . Higher levels of physical activity may also reduce systemic inflammation by lowering the levels of pro-inflammatory factors, such as Creactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-a) 33,35,36 . Finally, emerging evidence suggests that the gut microbiome may play an important role in the physical activity and cancer relationship. ...
Article
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Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.
... Many studies have reported that exercise training reduces inflammatory markers throughout the body. 26 In this study, above all, exergame group showed higher attendance and adherence than the treadmill group. Although the enjoyment scale was not measured in this study, it was considered that exergaming provided better enjoyment and motivation to patients than treadmill exercise. ...
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Objective: Recently, exergames have been used an exercise modality as aerobic fitness activities. However, evidence of its effectiveness on cardiovascular (CV)-related risk factors remain unclear. Hypothesis: We evaluate the effects of exergaming on CV-related risk factors compared with traditional aerobic exercise in high CV risk patients. Methods: Sixty-five postmenopausal women with high CV risk were randomized among exergame (n = 22), treadmill (n = 22), and control (n = 21) groups. The exergame group was engaged in the running-based exergame using Exer Heart and the treadmill group walked or jogged on a treadmill. Cardiorespiratory fitness, flow-mediated dilation, endothelial progenitor cells (EPCs), epicardial fat thickness, metabolic parameters, and anthropometric parameters were measured in patients before and 12 weeks after the training. Results: Exergaming significantly improved VO2 peak (P < .001; different from control, P < .05), flow-mediated dilation (P < .001; different from control, P < .05), EPCs (CD34/CD117+ , P < .01). Treadmill exercise was effective at improving VO2 peak (P < .01; different from control, P < .05), flow-mediated dilation (P < .05), EPCs (CD34/CD117+ , P < .01; different from control P < .05). Epicardial fat thickness decreased after both exercise programs (exergame, P < .01; treadmill, P < .01; no different from control). Conclusion: Exergaming showed similar effects to traditional aerobic exercise in improving cardiorespiratory fitness and endothelial function in postmenopausal women with high CV risk. These findings suggest that the exergames may serve as an alternative to conventional aerobic exercises for prevention and treatment in high CV risk patients.
... The beneficial effect of PE has been provided in animal studies and human trials, showing an impact on both systemic [14,85] and specific reduction of visceral fat mass [86,87], protecting against chronic inflammation-associated disease [88]. Several mechanisms have been proposed to explain the beneficial anti-inflammatory effect of PE. ...
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Adipose tissue accumulation is an independent and modifiable risk factor for cardiovascular disease (CVD). The recent CVD European Guidelines strongly recommend regular physical exercise (PE) as a management strategy for prevention and treatment of CVD associated with metabolic disorders and obesity. Although mutations as well as common genetic variants, including the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, are associated with increased body weight, eating and neuropsychiatric disorders, and myocardial infarction, the effect of this polymorphism on adipose tissue accumulation and regulation as well as its relation to obesity/thrombosis remains to be elucidated. Here, we showed that white adipose tissue (WAT) of humanized knock-in BDNFVal66Met (BDNFMet/Met) mice is characterized by an altered morphology and an enhanced inflammatory profile compared to wild-type BDNFVal/Val. Four weeks of voluntary PE restored the adipocyte size distribution, counteracted the inflammatory profile of adipose tissue, and prevented the prothrombotic phenotype displayed, per se, by BDNFMet/Met mice. C3H10T1/2 cells treated with the Pro-BDNFMet peptide well recapitulated the gene alterations observed in BDNFMet/Met WAT mice. In conclusion, these data indicate the strong impact of lifestyle, in particular of the beneficial effect of PE, on the management of arterial thrombosis and inflammation associated with obesity in relation to the specific BDNF Val66Met mutation.
... We previously demonstrated that treating Tg-SwDI mice with minocycline reduces inflammation and ameliorates behavioral deficits in the absence of altered amyloid pathology [30], providing further evidence that interventions targeting neuroinflammation may have therapeutic potential. Our current findings are in agreement with previous studies that have shown that exercise reduces innate immunity [53] and inflammatory cytokine expression in healthy mice and mouse models of AD associated with improved cognitive performance [44,54,55], as well as in aging and AD clinical populations [56][57][58]. It is likely that CVE reduces microglial activation (either in quantity of microglia or degree of reactivity). ...
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Background: Cardiovascular exercise (CVE) has been shown to be protective against cognitive decline in aging and the risk for dementias, including Alzheimer's Disease (AD). CVE has also been shown to have several beneficial effects on brain pathology and behavioral impairments in mouse models of AD; however, no studies have specifically examined the effects of CVE on cerebral amyloid angiopathy (CAA), which is the accumulation of amyloid-beta (Aβ) in the cerebral vasculature. CAA may be uniquely susceptible to beneficial effects of CVE interventions due to the location and nature of the pathology. Alternatively, CVE may exacerbate CAA pathology, due to added stress on already compromised cerebral vasculature. Methods: In the current study, we examined the effects of CVE over many months in mice, thereby modeling a lifelong commitment to CVE in humans. We assessed this voluntary CVE in Tg-SwDI mice, a transgenic mouse model of CAA that exhibits behavioral deficits, fibrillar vascular Aβ pathology, and significant perivascular neuroinflammation. Various "doses" of exercise intervention (0 h ("Sedentary"), 1 h, 3 h, 12 h access to running wheel) were assessed from ~ 4 to 12 months of age for effects on physiology, behavior/cognitive performance, and pathology. Results: The 12 h group performed the greatest volume of exercise, whereas the 1 h and 3 h groups showed high levels of exercise intensity, as defined by more frequent and longer duration running bouts. Tg-SwDI mice exhibited significant cerebral vascular Aβ pathology and increased expression of pro-inflammatory cytokines as compared to WT controls. Tg-SwDI mice did not show motor dysfunction or altered levels of anxiety or sociability compared to WT controls, though Tg-SwDI animals did appear to exhibit a reduced tendency to explore novel environments. At all running levels, CAA pathology in Tg-SwDI mice was not significantly altered, but 12-h high-volume exercise showed increased insoluble Aβ burden. However, CVE attenuated the expression of pro-inflammatory cytokines TNF-α and IL-6 and was generally effective at enhancing motor function and reducing anxiety-like behavior in Tg-SwDI mice, though alterations in learning and memory tasks were varied. Conclusions: Taken together, these results suggest that CAA can still develop regardless of a lifespan of substantial CVE, although downstream effects on neuroinflammation may be reduced and functional outcomes improved.
... A recent metaanalysis showed that increased social support and better social integration are associated with lower levels of circulating IL-6 and CRP [65]. Finally, PA may lead to engagement in more healthful behaviors [52], such as longer sleep duration and better quality sleep, or engaging in more physical activity [30,71]. These and other potential mediators between affect and health could be examined in future research using salivary markers of inflammation. ...
Article
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Background: Emerging evidence suggests that higher circulating levels of inflammatory biomarkers in blood are associated with higher negative affect (NA) and lower positive affect (PA). To our knowledge, the unique associations between NA and PA in daily life and salivary biomarkers of inflammation have not been examined. This study examined these associations in young adults. Methods: Measures of NA and PA were created from aggregated daily measures of affect (morning and evening ratings averaged across 14 days). We investigated associations between these measures and salivary C-reactive protein (CRP) and interleukin (IL)-6 in a sample of 108 young adults (60% female; mean age = 20.45 ± 1.47), a subset of whom had self-reported chronic back pain (n=49). CRP and IL-6 were determined from saliva obtained at the end of the daily diary period. Results: After covarying for age, gender, body mass index, chronic pain status, salivary flow rate, and NA, higher PA was associated with lower salivary CRP (β = -0.02, 95% CI [-0.03, -0.00] sr2 =.06, p=.01) but not IL-6; removing NA from this model did not change results. In a model with the same covariates (and PA), NA was not significantly related to CRP or IL-6. Chronic back pain status and gender did not moderate results. Conclusions: Findings suggest that higher PA may be associated with lower salivary CRP in young adults, even after accounting for NA and demographic characteristics. Findings highlight the utility of assessing emotional states in relation to salivary markers of inflammation in future biobehavioral research.
Chapter
Diabetes mellitus, referred to simply as diabetes, is a serious metabolic disorder that affects millions of people worldwide [1, 2]. It is caused by defects in insulin production, insulin secretion, and insulin signaling, all of which result in abnormally high blood sugar levels [3]. Diabetic patients usually develop serious secondary complications, especially involving the microvasculature but also cardiovascular disease, retinal damage, nerve damage, and kidney failure [4]. The two principal idiopathic forms of diabetes are known as types 1 and 2. Type 1 diabetes (T1D) is due to an autoimmune attack that leads to self-destruction of the insulin-producing β-cells of the pancreas. Type 2 diabetes (T2D) is caused by defects in insulin action and production, leading to insulin resistance, dyslipidemia, and impaired insulin secretion.KeywordsMetabolic diseasesDiabetesPeripheral inflammationAdipose inflammationIslet inflammationmiRNA
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Based on mounting clinical and translational evidence demonstrating the impact of exogenously administered inflammatory stimuli on the brain and behavior, increased endogenous inflammation has received attention as one pathophysiologic process contributing to psychiatric illnesses and particularly depression. Increased endogenous inflammation is observed in a significant proportion of depressed patients and has been associated with reduced responsiveness to standard antidepressant therapies. This chapter presents recent evidence that inflammation affects neurotransmitters and neurocircuits to contribute to specific depressive symptoms including anhedonia, motor slowing, and anxiety, which may preferentially improve after anti-cytokine therapies in patients with evidence of increased inflammation. Existing and novel pharmacological strategies that target inflammation or its downstream effects on the brain and behavior will be discussed in the context of a need for intelligent trial design in order to meaningfully translate these concepts and develop more precise therapies for depressed patients with increased inflammation.KeywordsInflammationCytokinesDepressionAnhedoniaDopamineGlutamateAntidepressants
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The purpose of this article is to investigate the role of the AMP-kinase pathway (AMPK pathway) in the induction of a concomitant set of health benefits by exercise, numerous drugs, and health ingredients, all of which are adversely affected by ageing. Despite the AMPK pathway being frequently mentioned in relation to both these health effects and ageing, it appears challenging to understand how the activation of a single biochemical pathway by various treatments can produce such a diverse range of concurrent health benefits, involving so many organs. We discovered that the AMPK pathway functions as an integrated stress response system because of the presence of a feedback loop in it. This evolutionary conserved stress response system detects changes in AMP/ATP and NAD/NADH ratios, as well as the presence of potential toxins, and responds by activating a common protective transcriptional response that protects against aging and promotes longevity. The inactivation of the AMPK pathway with age most likely explains why ageing has a negative impact on the above-mentioned set of health benefits. We conclude that the presence of a feedback loop in the AMP-kinase pathway positions this pathway as an AMPK-ISR (AMP Kinase-dependent integrated stress response) system that responds to almost any type of (moderate) environmental stress by inducing various age-related health benefits and longevity.
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In this chapter, we describe the converging lines of evidence indicating that organisms have had the ability to mount inflammatory and related immune responses since the beginning of life on earth. We can trace our own ability to mount inflammatory and related immune responses through the lineages of our predecessors and symbiotic relationships that we have formed with other organisms over the hundreds of millions of years of our evolutionary history. This has culminated in a repertoire of classic inflammatory responses consisting of pain, redness, heat, and swelling that humans described many thousands of years ago. We describe the great variability and common threads that exist across all life forms that undergird their ability to detect and defend themselves against threats coming from a wide variety of forces. We also describe important connection between the inflammatory response and the innate immune response that we see in all animals, including humans. Going back in time, it becomes clear that our own adaptive abilities are related to both progenitors (organisms that are now considered to be well established as part of our genetic and evolutionary lineage) and microorganisms with which we have developed commensal/symbiotic relationships over our evolutionary histories. The descriptions of inflammation from ancient human history provide an observational framework on which scientific developments over the last several hundred years have begun to fill in the blanks of how these complex systems are coordinated. This includes an understanding of how our inflammatory and innate immune systems have evolved, how the adaptive immune system has developed as part of a highly successful system of immunological reconnaissance, and the intercellular messaging necessary to orchestrate these complicated response systems that can react quickly and effectively to danger and threats. Finally, we set the stage for understanding the role of nutrition in determining whether an acute inflammatory/innate immune response occurs or whether the organism is doomed (or, rather, dooms itself) to live in a state of chronic, systemic inflammation wherein a competent inflammatory and immune response is compromised, and quality and duration of life are diminished.
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The immune-acquired responses after vaccination vary depending on the type of vaccine and the individual. The purpose of this study was to investigate the relationship between the acquisition of immunity and the side effects, health status, and lifestyle after completion of the second dose of AZD1222. Blood samples were collected after a second dose of AZD1222. The Euroimmun Anti-SARS-CoV-2 ELISA (IgG) for anti-S1 antibody, the cPASS SARS-CoV-2 neutralizing antibody detection kit for the surrogate virus neutralization test, and the T-spot Discovery SARS-CoV-2 kit were used to identify cellular immunogenicity. Patient experience of adverse effects was investigated using questionnaires. Information on health status and lifestyle were collected from the most recent health checkup data. Generally, females experience more reactogenicity in both intensity and duration. The rash of the first shot and chills of the second shot were associated with humoral immunity. However, comprehensive adverse effects had no correlation with humoral and cellular immunity. The T-spot-positive group had a higher creatinine level, which reflects muscle mass, than the T-spot-negative group. Males presented a higher level of T-spot assays. Body mass index and age were negatively correlated with the T-spot assay and anti-S1 antibody, respectively. Immune acquisition after the second AZD1222 shot was not associated with reactogenicity. However, individuals’ sex, age, and BMI were found to be associated with immunogenicity after vaccination.
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Background Physical activity (PA) has beneficial effects on health and health-related quality of life (HRQoL), which is a protective factor of illness and mortality. The purpose of this examination was to investigate if self-reported and device-based measures of PA were related to HRQoL in adolescents. Methods Participants (N = 1565; 54.3% female; Mage = 14.37 years, SDage = 1.99) were recruited from 167 sample points across Germany. Adolescents self-reported their PA, supplemented by a 1-week examination of device-based PA using accelerometry. Additionally, they completed the multidimensional KIDSCREEN-27 to assess HRQoL. Results Results showed that self-reported PA was correlated with overall HRQoL, Physical Well-Being, Psychological Well-Being, Social Support & Peers, and School Environment, whereas device-based PA was only correlated with Physical as well as Psychological Well-Being. Further, self-reported PA significantly predicted all facets of HRQoL except for Autonomy and Parent Relations, whereas device-based PA solely heightened the amount of explained variance in the Physical Well-Being subscale. Conclusions Findings demonstrate the importance of self-reported PA as it is related to almost all facets of HRQoL. Both measures of PA are not congruent in their relationship with HRQoL and thus implications have to be carefully considered. Future studies should investigate the direct effect of PA on HRQoL and health in a longitudinal approach to account for the causality of effects.
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Safflower is the oldest cultivated crop, typically grown at a small-scale level. Each part of this crop has multiple uses ranging from oil, foods, flavors, coloring agents, dyes, and medicinal benefits. Safflower crop can tolerate salinity and drought effectively. Various techniques are used to harvest the oil ranging from mechanical to supercritical fluid extraction; the extracted oil is rich in oleic and linoliec acids. The functional attributes of safflower include treatment of atherosclerosis, menopause, skin infection, and bone-related disorders. Recently, safflower oil is used in encapsulate sensitive bioactive compounds for nutrients delivery systems. This chapter highlights safflower chemical characteristics in combination with health benefits.
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Background: Inflammation is the body’s response to various diseases that also happens after strenuous exercise. Previous studies showed significant effect of fish oil on reducing inflammation in patients but its effect on exercise inflammation and muscular performance is not well understood. Therefore, the aim of this study was to investigate the effect of 4-weeks fish oil supplementation on inflammatory mediators and muscular performance in response to exhaustive exercise. Methods: For this purpose, 16 healthy men (age: 26.90±2.64 yrs, weight: 78.33±10.42 kg, height: 175.80±4.89 cm, body fat percent: 18.40±5.46%) voluntarily participated and were assigned in fish oil (FO=9) and corn oil (CO=7) groups and consumed 6 gr/day supplements for 4 weeks. Levels of TNF-α, IL-10 and salivary cortisol were investigated using ELISA method. In addition, MVC of the tibilias anterior muscle was also assessed. Blood and saliva samples and MVC assessments were performed before and after exercise both in pre- and post-supplementation periods. Results: Our results showed significant decrease in baseline values of TNF-α and IL-10 and increase in baseline values of MVC of FO group after supplementation (P<0.05). In addition, significant differences were observed between IL-10 (F=9.17, P=0.017) and MVC (F=4.79, P=0.046) changes of participants after supplementation. However, there wasn’t significant differences in salivary cortisol values after supplementation or exercise (P>0.05). Conclusion: Our results showed significant effect of FO supplementation on reducing inflammation either before or after exercise that can lead to increase in muscular performance. However, its exact molecular pathways need more investigation.
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The aim of the present study was to determine if the training status decreases inflammation, slows down senescence and preserves telomeres health in skeletal muscle in older compared to younger subjects, with a specific focus on satellite cells. Analyses were conducted on skeletal muscle and cultured satellite cells from vastus lateralis biopsies (n=34) of male volunteers divided into four groups: young sedentary (YS), young trained cyclists (YT), old sedentary (OS) and old trained cyclists (OT). The senescence state and inflammatory profile were evaluated by telomere dysfunction-induced foci (TIF) quantification, senescence associated b-gal (SA-b-Gal) staining and qRT-PCR. Independently of the endurance training status, TIF levels (+35%, P < 0.001) and the percentage of SA-b-Gal positive cells (+30%, P < 0.05) were higher in cultured satellite cells of older compared to younger subjects. p16 (4-5 fold) and p21 (2-fold) mRNA levels in skeletal muscle were higher with age but unchanged by the training status. Aging induced higher CD68 mRNA levels in human skeletal muscle (+102%, P = 0.009). Independently of age, both trained groups had lower IL-8 mRNA levels (-70%, P = 0.011) and tended to have lower TNFa mRNA levels (-40%, P = 0.10) compared with the sedentary subjects. All together, we found that the endurance training status did not slow down senescence in skeletal muscle and satellite cells in older compared to younger subjects despite reduced inflammation in skeletal muscle. These findings highlight that the link between senescence and inflammation can be disrupted in skeletal muscle.
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Medical advances in the treatment of cancer have contributed to less invasive and more targeted strategies, as well as increasing effectiveness in terms of survival. However, receiving cancer treatment is also associated with a range of side effects, which persist throughout the post-treatment cancer survivorship phase or which may appear months to years after treatment cessation. Further, persistent and late treatment-related side effects, alongside disease- and treatment-related adverse changes in function and quality of life, are interrelated and influence survival. Physical activity, including exercise, represents an efficacious strategy for improving quality of survival, through prevention and better management of treatment-related sequelae and improvements in function, quality of life, and pre-existing comorbidities or other chronic disease, and has potential for improving quantity of survival (all-cause and cancer-specific mortality). This chapter will introduce survivorship concerns experienced during the post-treatment phase and will briefly discuss the role of physical activity, including exercise, post-treatment to end of life.
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Background: The effects of exercise on brain function are widely known; however, there is a need for inexpensive, practical solutions for monitoring and metering the activity of multiple mice. New method: A contoured running wheel that has a built-in radio-frequency identification (RFID) receiver to monitor the activity of several mice in a single cage is presented. This system is scalable up to 20 cages, the interface is easy to use, and the wheel can be dynamically locked so that each group-housed mouse receives a set exercise regimen. Results: We were able to reliably monitor three mice that were group-housed. We were able to reliably meter the amount of exercise performed by the mice using the servo-controlled lock. Comparison with existing methods: Current methods allow a wheel to be locked when a set distance is reached. However, an issue with this method is that the set distance includes the cumulative activity of all mice in the cage so one mouse could contribute a disproportionate amount to the total distance. Our solution ensures that the wheel is locked when an individual mouse reaches the target distance, but remains unlocked for individuals that have not reached the programmed distance. Conclusions: The dynamic locking wheel (DynaLok) is designed to allow a researcher to provide individually designed exercise plans for multi-housed mice; therefore, users are able to house mice conventionally rather than in individual cages. DynaLok reduces animal housing costs, allows for new experimental exercise regimens to be developed, and is scalable and cost-effective.
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Background & Aims: Deaths from cancer metastases are rising, and the process involved in metastasis is the transmission of epithelial to mesenchymal mood. Therefore, the purpose of this study was to investigate the influence of interval training on the expression of mesenchyme biomarkers, cachexia, and tumor volume in mice with breast cancer. Materials & Methods: Thirty-two female BALB/c mice were randomly divided into four groups: Exercise-Tumor-Exercise, Rest-Tumor-Rest, Rest-Tumor-Exercise, and Exercise-Tumor-Rest. Interval training was performed six weeks before and four weeks after the tumorigenesis. All mice were cancerous by subcutaneous injection of the 4T-1 cell line. Real-time PCR method was used to evaluate the expression of TGF-β. Also, weight test and the Inverted Screen Test were carried out to estimate muscle functions in mice. Data were analyzed with one-way ANOVA and HSD-Post Hoc test with P ≤ 0.05. Results: The results showed a significant decrease in gene expressions of TGF-β in Exercise-Tumor-Exercise group in comparison with the Rest-Tumor-Rest group (P=0/005). Remarkable reduction of tumor volume was also observed in two training groups (Rest-Tumor-Exercise, Exercise-Tumor-Exercise) compared to the control group (Rest-Tumor-Rest) (p=0/0001). According to function tests' results, muscle functions were diminished due to cancer (p=0/003). But it should be indicated that interval training can keep muscles in a normally-functioned state in cancer (P=0/045). Conclusion: Considering final results, a period of interval training can be used not only as a prevention method, but also to help cancer treatment and impede cachexia by tumor volume reduction, decrease mesenchymal biomarker gene expressions, and increase muscle strength functions.
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Introduction Many deaths from cancer are due to metastases, a process which involves the epithelial-mesenchymal transition (EMT). On the other hand, regular exercise plays an important role in inhibiting the progression of breast cancer. Therefore, the purpose of this study was to investigate the influence of interval training on the expression of VIM, the gene encoding for EMT biomarker vimentin, and tumor volume in mice with breast cancer.
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The age-associated dysregulation of the immune response contributes to higher incidences of infectious diseases in the aged. Of note, there is dysregulation of cytokines, including a change in T helper (Th) 1/Th2 cytokine balance and an increase in production of proinflammatory cytokines. Synthesis of many cytokines is influenced by changes in the cellular oxidant/antioxidant balance. Because vitamin E supplementation reduces oxidative stress and improves the immune response in the aged, a series of experiments was conducted to determine the effect of supplementation with vitamin E and other antioxidants on resistance to influenza infection in aged mice and the role of cytokines in vitamin E—induced increase in resistance to influenza infection. The results of these studies plus findings by other investigators on the effects of age and antioxidants on production of cytokines in human and animal models are reviewed.
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The metabolic syndrome is characterized by a clustering, in free-living populations, of cardiovascular and diabetes risk factors generally linked to insulin resistance, obesity and central obesity. Consonant with the well-established inflammatory pathogenesis of atherosclerotic disease, the metabolic syndrome is now being investigated in relation to its inflammatory nature. We present cross-sectional findings demonstrating that markers of inflammation correlate with components of the metabolic syndrome, and prospective findings of the ARIC Study indicating that markers of inflammation and endothelial dysfunction predict the development of diabetes mellitus and weight gain in adults. We present biological evidence to suggest that chronic activation of the innate immune system may underlie the metabolic syndrome, characterizing the common soil for the causality of type 2 diabetes mellitus and cardiovascular disease. Better understanding of the role of the innate immune system in these diseases may lead to important advances in the prediction and management of diabetes and cardiovascular disease.
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Obesity is an independent risk factor for cardiovascular disease, which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue. To determine the effect of a program of changes in lifestyle designed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance. Randomized single-blind trial conducted from February 1999 to February 2002 at a university hospital in Italy. One hundred twenty premenopausal obese women (body mass index > or =30) aged 20 to 46 years without diabetes, hypertension, or hyperlipidemia. The 60 women randomly assigned to the intervention group received detailed advice about how to achieve a reduction of weight of 10% or more through a low-energy Mediterranean-style diet and increased physical activity. The control group (n = 60) was given general information about healthy food choices and exercise. Lipid and glucose intake; blood pressure; homeostatic model assessment of insulin sensitivity; and circulating levels of interleukin 6 (IL-6), interleukin 18 (IL-18), C-reactive protein (CRP), and adiponectin. After 2 years, women in the intervention group consumed more foods rich in complex carbohydrates (9% corrected difference; P<.001), monounsaturated fat (2%; P =.009), and fiber (7 g/d; P<.001); had a lower ratio of omega-6 to omega-3 fatty acids (-5; P<.001); and had lower energy (-310 kcal/d; P<.001), saturated fat (-3.5%; P =.007), and cholesterol intake (-92 mg/d; P<.001) than controls. Body mass index decreased more in the intervention group than in controls (-4.2; P<.001), as did serum concentrations of IL-6 (-1.1 pg/mL; P =.009), IL-18 (-57 pg/mL; P =.02), and CRP (-1.6 mg/L; P =.008), while adiponectin levels increased significantly (2.2 microg/mL; P =.01). In multivariate analyses, changes in free fatty acids (P =.008), IL-6 (P =.02), and adiponectin (P =.007) levels were independently associated with changes in insulin sensitivity. In this study, a multidisciplinary program aimed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance.
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Insulin resistance arises from the inability of insulin to act normally in regulating nutrient metabolism in peripheral tissues. Increasing evidence from human population studies and animal research has established correlative as well as causative links between chronic inflammation and insulin resistance. However, the underlying molecular pathways are largely unknown. In this report, we show that many inflammation and macrophage-specific genes are dramatically upregulated in white adipose tissue (WAT) in mouse models of genetic and high-fat diet-induced obesity (DIO). The upregulation is progressively increased in WAT of mice with DIO and precedes a dramatic increase in circulating-insulin level. Upon treatment with rosiglitazone, an insulin-sensitizing drug, these macrophage-originated genes are downregulated. Histologically, there is evidence of significant infiltration of macrophages, but not neutrophils and lymphocytes, into WAT of obese mice, with signs of adipocyte lipolysis and formation of multinucleate giant cells. These data suggest that macrophages in WAT play an active role in morbid obesity and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance. We propose that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue.
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Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We found that the expression of 1,304 transcripts correlated significantly with body mass. Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass. Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80+) was significantly and positively correlated with both adipocyte size and body mass. Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68. Bone marrow transplant studies and quantitation of macrophage number in adipose tissue from macrophage-deficient (Csf1op/op) mice suggest that these F4/80+ cells are CSF-1 dependent, bone marrow-derived adipose tissue macrophages. Expression analysis of macrophage and nonmacrophage cell populations isolated from adipose tissue demonstrates that adipose tissue macrophages are responsible for almost all adipose tissue TNF-alpha expression and significant amounts of iNOS and IL-6 expression. Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals.
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For examining the effects of moderate exercise training on peripheral glucose effectiveness (S(g)(2)*), insulin sensitivity (S(i)(2)*), and endogenous glucose production (EGP), seven men and one woman (24.8 +/- 1.8 years) participated in cycle ergometer training at lactate threshold intensity for 60 min/day, 5 days/week for 12 weeks. Stable-labeled frequently sampled intravenous glucose tolerance tests were performed before and 16 h and 1 week after the last training session. S(g)(2)* (pre 0.71 +/- 0.03 x 10(-2), 16 h 0.85 +/- 0.02 x 10(-2) dl. kg(-1). min(-1)) and S(i)(2)* (pre 12.6 +/- 2.6 x 10(-4), 16 h 19.7 +/- 3.3 x 10(-4) dl. kg(-1). min(-1). [ micro U/ml](-1)), analyzed using the two-compartment minimal model, were significantly elevated 16 h after the last training session. The elevated S(g)(2)* remained higher despite the cessation of exercise training for 1 week (1.00 +/- 0.03 x 10(-2) dl. kg(-1). min(-1)). EGP was suppressed within 20 min after glucose bolus, and the suppression of EGP was followed by their overshoot. The time course of EGP during the intravenous glucose tolerance test remained similar after the training period. In conclusion, moderate exercise training at lactate threshold improves not only peripheral insulin sensitivity but also peripheral glucose effectiveness with no change in the effect of glucose and/or insulin to suppress EGP in healthy humans.
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Persistent, low-grade inflammation is an independent predictor of several chronic diseases and all-cause mortality. The intention of this study was to determine the independent and combined effects of diet-induced weight loss and exercise on markers of chronic inflammation. Three hundred sixteen community-dwelling, older (> or = 60 y), overweight or obese [body mass index (in kg/m2) > or = 28], sedentary men and women with radiographic evidence of knee osteoarthritis were randomly assigned to four 18-mo treatments: healthy lifestyle control, diet-induced weight loss, exercise, and diet plus exercise. The exercise intervention consisted of combined weight training and walking for 1 h 3 times/wk. The weight-loss intervention consisted of a weekly session with a registered dietitian to provide education and support for lowering energy intake. The diet-induced weight-loss intervention resulted in significantly greater reductions in concentrations of C-reactive protein (P = 0.01), interleukin 6 (P = 0.009), and soluble tumor necrosis factor alpha receptor 1 (P = 0.007) than did no weight-loss treatment. Changes in soluble tumor necrosis factor alpha receptor 1 but not in C-reactive protein or interleukin 6 correlated with changes in body weight. Exercise training did not have a significant effect on these inflammatory biomarkers, and there was no significant interaction between weight loss and exercise training. These findings provide evidence from a randomized controlled trial that a dietary intervention designed to elicit weight loss reduces overall inflammation in older, obese persons. Additional studies are needed to assess the effects of different modes and intensities of exercise on inflammation.
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The purpose of this study was to determine whether a hypocaloric diet with and without exercise training is effective in reducing plasma C-reactive protein, IL-6, TNFalpha, and their soluble receptors (sIL-6R, sTNFR1, and sTNFR2), and whether changes in these inflammatory markers are related to changes in regional lipolysis in obese (body mass index, 32.78 +/- 4.73) postmenopausal women (diet alone, n = 17; diet plus exercise, n = 17). All inflammatory markers were measured by an ELISA method. In vitro lipolysis was evaluated by measuring glycerol release using a one-step enzymatic fluorometric technique. Six months of diet and diet plus exercise decreased total and abdominal fat to a similar degree. Diet plus exercise, but not diet alone, decreased plasma levels of C-reactive protein, IL-6, sIL-6R, and sTNFR1 and increased basal and postreceptor stimulated lipolysis in both abdominal and gluteal regions. Changes in abdominal stimulated lipolysis correlated significantly with changes in plasma IL-6 (r = -0.39) and TNFR1 (r = -047). Thus, diet plus exercise training, but not diet alone, is effective in reducing chronic inflammation in obese postmenopausal women. In addition, modification of chronic inflammation is associated with changes in local adipose tissue metabolism in response to diet and exercise.
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In this study, we determined the effects of age and chronic treadmill running (16 wk; 5 days/wk; 45 min/day; 18-22 m/min) on resident peritoneal macrophage responsiveness to interferon-γ (IFN-γ) and lipopolysaccharide (LPS) in young (6 mo) and aged (22 mo) male BALB/cByJ mice by measuring cytolytic ability and production of reactive nitrogen products. Macrophages (>90% Mac-3+) were incubated with various concentrations of IFN-γ and LPS for 24 h. After washing, P815 tumor cells were utilized as targets in a 16-h51Cr release assay. We found that aging resulted in a significant reduction in the ability of macrophages to respond to the highest doses of IFN-γ and LPS and kill P815 cells (46 ± 4 vs. 34 ± 2% in young and old mice, respectively). Exercise training significantly increased macrophage cytolysis in both age groups (66 + 7 vs. 44 + 2% in young and old mice, respectively); this effect was larger in the young mice. Macrophages from young exercised mice also produced significantly (50-60%) more[Formula: see text]; there was a tendency for higher[Formula: see text] in old exercisers. The inducible nitric oxide synthase (iNOS) inhibitor NG-monomethyl-l-arginine (l-NMMA) significantly reduced macrophage cytolysis and [Formula: see text]production and completely abrogated exercise-induced increases in these measures. RT-PCR analysis revealed significantly higher iNOS mRNA levels in macrophages obtained from the exercise-trained mice and significantly lower iNOS mRNA in old compared with young mice. We conclude that aging reduces and exercise training increases the capacity of resident peritoneal macrophages to respond to IFN-γ and LPS with increased tumor cytolysis. Enhanced iNOS gene expression and[Formula: see text] production are likely the contributing mechanisms of the exercise-induced enhancement of cytolysis in young mice. Whilel-NMMA did block the exercise-induced increase in cytolysis, exercise did not increase[Formula: see text] or iNOS gene expression in the old mice, indicating perhaps the contribution of other cytolytic mechanisms in old mice.
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Objective: Plasma concentrations of interleukin-6 (IL-6), a proinflammatory cytokine produced and released in part by adipose tissue, are elevated in people with obesity and type 2 diabetes. Because recent studies suggest that markers of inflammation predict the development of type 2 diabetes, we examined whether circulating plasma IL-6 concentrations were related to direct measures of insulin resistance and insulin secretory dysfunction in Pima Indians, a population with high rates of obesity and type 2 diabetes. Research Methods and Procedures: Fasting plasma IL-6 concentrations (enzyme-linked immunosorbent assay), body composition (DXA), insulin action (M; hyperinsulinemic euglycemic clamp), and acute insulin secretory responses to glucose (25 g intravenous glucose tolerance test) were measured in 58 Pima Indians without diabetes (24 women, 34 men). Results: Fasting plasma IL-6 concentrations were positively correlated with percentage of body fat (r = 0.26, p = 0.049) and negatively correlated with M (r = −0.28, p = 0.031), but were not related to acute insulin response (r = 0.13, p = 0.339). After adjusting for percentage of body fat, plasma IL-6 was not related to M (partial r = −0.23, p = 0.089). Discussion: Fasting plasma IL-6 concentrations are positively related to adiposity and negatively related to insulin action in Pima Indians. The relationship between IL-6 and insulin action seems to be mediated through adiposity.
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A physically active lifestyle incurs many health benefits. One recently recognized benefit of regular moderate exercise is stress reduction. The current review develops the hypothesis that physical activity may prevent stress-induced suppression of the immune system and suggests an immunophysiological mechanism (sympathetic nervous system constraint) for this effect.
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The concept of an alternative pathway of macrophage activation has stimulated interest in its definition, mechanism, and functional significance in homeostasis and disease. We assess recent research in this field, argue for a restricted definition, and explore pathways by which the T helper 2 (Th2) cell cytokines interleukin-4 (IL-4) and IL-13 mediate their effects on macrophage cell biology, their biosynthesis, and responses to a normal and pathological microenvironment. The stage is now set to gain deeper insights into the role of alternatively activated macrophages in immunobiology.
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Printout. Thesis (M.S.)--University of Illinois at Urbana-Champaign, 1999. Includes bibliographical references.
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The ability of macrophages to secrete reactive oxygen intermediates, as well as reactive nitrogen intermediates, correlates closely with their capacity to perform two critical effector functions: intracellular killing of microorganisms and lysis of tumor cells. In this study, age-associated changes in the ability of caseinate-elicited peritoneal macrophages to release hydrogen peroxide were determined. Macrophages from aged BALB/c mice produced 50% less hydrogen peroxide than those from young mice in response to PMA or opsonized zymosan. In contrast, the production of macrophage-activating cytokines including IFN-gamma was not diminished in splenocyte supernatants from the aged group. Furthermore, no difference was detected in surface expression of IFN-gamma receptor in old and young mice. Macrophage responses to IFN-gamma, however, declined with aging. In vitro, IFN-gamma-induced release of hydrogen peroxide and nitric oxide was 50% lower in old mice than in young mice. IFN-gamma-induced tyrosine phosphorylation of MAPK, an early activation event, was undetectable in macrophages from the aged mice. These data demonstrate that diminished responses of macrophages to activating signals are one aspect of the impaired immune response in aged mice.
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Obesity is frequently associated with insulin resistance and abnormal glucose homeostasis. Recent studies in animal models have indicated that TNF-alpha plays an important role in mediating the insulin resistance of obesity through its overexpression in fat tissue. However, the mechanisms linking obesity to insulin resistance and diabetes in humans remain largely unknown. In this study we examined the expression pattern of TNF-alpha mRNA in adipose tissues from 18 control and 19 obese premenopausal women by Northern blot analysis. TNF-alpha protein concentrations in plasma and in conditioned medium of explanted adipose tissue were measured by ELISA. Furthermore, the effects of weight reduction by dietary treatment of obesity on the adipose expression of TNF-alpha mRNA were also analyzed in nine premenopausal obese women, before and after a controlled weight-reduction program. These studies demonstrated that obese individuals express 2.5-fold more TNF-alpha mRNA in fat tissue relative to the lean controls (P < 0.001). Similar increases were also observed in adipose production of TNF-alpha protein but circulating TNF-alpha levels were extremely low or undetectable. A strong positive correlation was observed between TNF-alpha mRNA expression levels in fat tissue and the level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance. Finally, body weight reduction in obese subjects which resulted in improved insulin sensitivity was also associated with a decrease in TNF-alpha mRNA expression (45%, P < 0.001) in fat tissue. These results suggest a role for the abnormal regulation of this cytokine in the pathogenesis of obesity-related insulin resistance.
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This study was initiated to determine the effect of physical exercise on the in vivo tumor necrosis factor-alpha (TNF) response to Escherichia coli lipopolysaccharide (LPS). Rats familiarized with treadmill running and surgically implanted with vascular catheters were either not exercised or exercised to near exhaustion (mean run time of 102 +/- 13 min) before intravenous LPS challenge (1 mg/kg; lethality of dose is 10-20% in 24 h). Compared with time-matched nonexercised control rats, exercised rats had increased heart rates, plasma lactate, and plasma corticosterone and decreased plasma glucose at the conclusion of exercise. In response to LPS, both groups became hypotensive, exhibited transient hyperglycemia, and sustained hyperlactacidemia. By 30 min post-LPS, plasma corticosterone levels were similar in the two groups. Nonexercised rats exhibited a normal plasma TNF response to LPS with the peak value (10,400 +/- 2,000 U/ml) occurring 90 min after LPS challenge. In contrast, the TNF response in rats exercised before LPS administration was blunted to 17% of the nonexercised group, with the peak occurring at an earlier time after LPS. Addition of recombinant murine TNF to postexercise plasma was fully expressed. The TNF response remained attenuated when LPS was administered up to 6 h after completion of exercise, but it returned to normal in rats allowed to recover for 24 h. The results demonstrate that exercise, perhaps as a stress modality, markedly suppresses the systemic TNF response that is normally observed in response to LPS challenge.
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Recent data have suggested a key role for tumor necrosis factor (TNF)-alpha in the insulin resistance of obesity and non-insulin-dependent diabetes mellitus (NIDDM). TNF-alpha expression is elevated in the adipose tissue of multiple experimental models of obesity. Neutralization of TNF-alpha in one of these models improves insulin sensitivity by increasing the activity of the insulin receptor tyrosine kinase, specifically in muscle and fat tissues. On a cellular level, TNF-alpha is a potent inhibitor of the insulin-stimulated tyrosine phosphorylations on the beta-chain of the insulin receptor and insulin receptor substrate-1, suggesting a defect at or near the tyrosine kinase activity of the insulin receptor. Given the clear link between obesity, insulin resistance, and diabetes, these results strongly suggest that TNF-alpha may play a crucial role in the systemic insulin resistance of NIDDM. This may allow for new treatments of disorders involving resistance to insulin.
Article
In this study, we determined the effects of age and chronic treadmill running (16 wk; 5 days/wk; 45 min/day; 18-22 m/min) on resident peritoneal macrophage responsiveness to interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) in young (6 mo) and aged (22 mo) male BALB/cByJ mice by measuring cytolytic ability and production of reactive nitrogen products. Macrophages (>90% Mac-3(+)) were incubated with various concentrations of IFN-gamma and LPS for 24 h. After washing, P815 tumor cells were utilized as targets in a 16-h 51Cr release assay. We found that aging resulted in a significant reduction in the ability of macrophages to respond to the highest doses of IFN-gamma and LPS and kill P815 cells (46 +/- 4 vs. 34 +/- 2% in young and old mice, respectively). Exercise training significantly increased macrophage cytolysis in both age groups (66 + 7 vs. 44 + 2% in young and old mice, respectively); this effect was larger in the young mice. Macrophages from young exercised mice also produced significantly (50-60%) more NO-2; there was a tendency for higher NO-2 in old exercisers. The inducible nitric oxide synthase (iNOS) inhibitor NG-monomethyl-L-arginine (L-NMMA) significantly reduced macrophage cytolysis and NO-2 production and completely abrogated exercise-induced increases in these measures. RT-PCR analysis revealed significantly higher iNOS mRNA levels in macrophages obtained from the exercise-trained mice and significantly lower iNOS mRNA in old compared with young mice. We conclude that aging reduces and exercise training increases the capacity of resident peritoneal macrophages to respond to IFN-gamma and LPS with increased tumor cytolysis. Enhanced iNOS gene expression and NO-2 production are likely the contributing mechanisms of the exercise-induced enhancement of cytolysis in young mice. While L-NMMA did block the exercise-induced increase in cytolysis, exercise did not increase NO-2 or iNOS gene expression in the old mice, indicating perhaps the contribution of other cytolytic mechanisms in old mice.
Article
Reactive oxygen (ROS) and nitrogen species (RNS) are continuously generated in the biological system and play an important role in a variety of physiological and pathological processes. There is evidence that physical exercise augments the generation of ROS/RNS. The present review discusses and compares insights into the generation and function of ROS/RNS such as superoxide, hydrogen peroxide, hypochloric acid, and nitric oxide released by leukocytes in response to exercise. Emphasis is placed on: (a) mechanisms and regulation of ROS/RNS generation in immunocompetent cells with respect to acute exercise and regular training; (b) damaging effects of ROS/RNS in terms of oxidative stress which may be causally involved in features such as exercise-induced damage to muscle tissue and leukocyte DNA; (c) (immuno-) modulating effects of ROS/RNS which include activation of transcription factors; (d) responses of antioxidant stress proteins to acute exercise and regular training; and (e) effects of antioxidants on exercise-induced changes in immune function. Available data suggests that ROS/RNS are involved in the inflammatory response to heavy exercise and therefore exert damaging effects. Several immune functions are influenced by actions of ROS/RNS, and it is hypothesized that adaption to regular training is also modulated in part by free radicals. Furthermore, regular training seems to reduce the capacity of leukocytes for oxidant release and leads to an adaptation of antioxidative mechanisms, which may contribute to a limitation of exercise-induced oxidative stress.
Article
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.
Article
In parallel to the Th1/Th2 paradigm, antigen-presenting cells (APC) are divided into classically activated APC (dendritic cells/effector macrophages) and alternatively activated APC (IL-4-induced, alternatively activated macrophages/IL-10-induced, immature dendritic cells). Alternatively activated APC share a special molecular repertoire including receptors of innate immunity with broad specificity for foreign antigen and anti-inflammatory cytokines such as IL-1Ra and alternative macrophage activation-associated CC-chemokine-1. Alternatively activated APC mediated tolerance and downregulated inflammation. Abuse of alternatively activated APC in support of infectious susceptibility or tumor immune escape is counteracted by the classical pathway. Thus, classically and alternatively activated APC secure the balance between proinflammatory and anti-inflammatory immune reactions.
Article
Previous studies have shown an abnormal expression of cellular adhesion molecules and cytokines in chronic heart failure, which may be related to endothelial dysfunction characterizing this syndrome. Our study investigates the effects of physical training on serum activity of some peripheral inflammatory markers associated with endothelial dysfunction, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with chronic heart failure. Serum levels of GM-CSF, MCP-1, sICAM-1 and sVCAM-1 were determined in 12 patients with stable chronic heart failure (ischaemic heart failure: 6/12, dilated cardiomyopathy: 6/12, New York Heart Association: II-III, ejection fraction: 24+/-2%) before and after a 12-week programme of physical training in a randomized crossover design. In addition, the functional status of chronic heart failure patients was evaluated by using a cardiorespiratory exercise stress test to measure peak oxygen consumption. Physical training produced a significant reduction in serum GM-CSF (28+/-2 vs 21+/-2 pg. ml(-1), P<0.001), MCP-1 (192+/-5 vs 174+/-6 pg. ml(-1), P<0.001), sICAM-1 (367+/-31 vs 314+/-29 ng. ml(-1), P<0.01) and sVCAM-1 (1247+/-103 vs 1095+/-100 ng. ml(-1), P<0.01) as well as a significant increase in peak oxygen consumption (14.6+/-0.5 vs 16.5+/-0.5 ml. kg(-1)min(-1), P<0.005). A significant correlation was found between the training-induced improvement in peak oxygen consumption and percentage reduction in soluble adhesion molecules sICAM-1 (r=-0.72, P<0.01) and sVCAM-1 (r=-0.67, P<0.02). Physical training affects beneficially peripheral inflammatory markers reflecting monocyte/macrophage-endothelial cell interaction. Training-induced improvement in exercise tolerance is correlated with the attenuation of the inflammatory process, indicating that inflammation may contribute significantly to the impaired exercise capacity seen in chronic heart failure.