Serum Interleukin-6 and Hemoglobin as Physiological Correlates in the Geriatric Syndrome of Frailty: A Pilot Study

Division of Geriatric Medicine and Gerontology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Journal of the American Geriatrics Society (Impact Factor: 4.57). 08/2002; 50(7):1268-71. DOI: 10.1046/j.1532-5415.2002.50315.x
Source: PubMed


To determine specific physiological correlates of the geriatric syndrome of frailty that warrant further investigation.
Population-based case-control study.
General Clinical Research Center at Johns Hopkins Bayview Medical Center.
Community-dwelling adults aged 74 and older from Baltimore, Maryland.
Frailty status was determined using a recently validated screening tool that consists of weight loss, fatigue, low levels of physical activity, and measurements of grip strength and walking speed. Serum interleukin-6 (IL-6) was measured using enzyme-linked immunosorbent assay, and standard complete blood count was performed using a Coulter counter.
Eleven frail and 19 nonfrail subjects with mean age +/- standard deviation of 84.9 +/- 6.7 vs 81.3 +/- 4.1 years, respectively, completed the study. The frail subjects had significantly higher serum IL-6 levels and significantly lower hemoglobin and hematocrit than the nonfrail subjects (4.4 +/-2.9 vs 2.8 +/- 1.6 pg/mL, 12.1 +/- 1.1 vs 13.9 +/- 1.0 g/dL, and 35.8% +/- 3.1% vs 40.6% +/- 2.8%, respectively). No significant difference was observed in mean corpuscular volume, red blood cell distribution width, or white blood cell and platelet counts between the frail and nonfrail groups. Furthermore, there was an inverse correlation between serum IL-6 level and hemoglobin (Pearson's correlation coefficient: -0.46) and hematocrit (-0.48) in the frail group but not in the nonfrail group.
These results suggest that frail subjects have evidence of inflammation and lower hemoglobin and hematocrit levels. This subclinical anemia is normocytic and is hence unlikely due to myelosuppression or iron deficiency and is potentially related to the increased chronic inflammatory state marked by serum IL-6 elevation. Further studies are indicated to better characterize the immune and hematological changes that underlie frailty.

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    • "Moreover, geriatric risk scores proved to be superior as compared to canonical surgical risk scores for the prediction of death and functional decline following TAVR [7]. As uniform and reproducible frailty assessment tools are not available, metabolomic signatures associated with the frailty phenotype including increased tryptophan degradation alongside elevated interleukin-6 and neopterin levels may be useful [8] [9] [10]. Neopterin, a pteridine derivative mainly produced by activated macrophages after induction by the Th1 cytokine interferon-γ has been associated with plaque vulnerability [11], and increased neopterin IJC Metabolic & Endocrine 10 (2016) 7–15 ⁎ Corresponding author at: Department of Cardiology, University Heart Center Zuerich, Raemistrasse 100 8091 Zuerich, Switzerland. "
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    ABSTRACT: Frailty and associated comorbidities are often prohibitive surgical risk factors in symptomatic severe aortic stenosis. Transcatheter aortic valve replacement (TAVR) is a viable treatment option for such patients. However, biomarkers providing a precise estimate of individual vulnerability and hence pre-interventional risk for mortality are not available in this heterogenous patient population. Neopterin, a pteridine synthesized by activated macrophages, has been associated with prevalent frailty in elderly patients. Moreover, immune activation-mediated tryptophan degradation has been suggested to reflect frailty and reduced life expectancy in diverse chronic disease states.
    Full-text · Article · Nov 2015 · IJC Metabolic and Endocrine
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    • "Moreover, the authors of the CHAMP study accepted that their results were unexpected, as high tissue expression of SIRT1 was generally considered to be beneficial, it was induced by CR and expected to be higher in younger animals. There are some biological parameters which have been used as biomarkers of frailty, namely inflammation (Leng et al., 2002, 2004, 2007, 2009), central adiposity, serum albumin, oxidative stress (Wu et al., 2009), vitamin-E (Ble et al., 2006), and 25 hydrooxy vitamin-D level (Hirani et al., 2013). These parameters are, however, nonspecific and do not indicate any mechanistic pathway. "
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    ABSTRACT: Frailty has emerged as a major health issue among older patients. A consensus on definition and diagnosis is yet to be achieved. Various biochemical abnormalities have been reported in frailty. Activation of sirtuins, a conserved family of NAD-dependent proteins, is one of the many mimics of calorie restriction which improves lifespan and health in experimental animals. In this cross-sectional study, we assessed the circulating sirtuin levels in 119 (59.5%) nonfrail and 81 (40.5%) frail individuals, diagnosed by Fried's criteria. Serum SIRT1, SIRT2, and SIRT3 were estimated by surface plasmon resonance (SPR) and Western blot. Serum sirtuins level in mean+SD; SIRT1 (nonfrail –4.67 ± 0.48 ng/μL; frail – 3.72 ± 0.48 ng/μL; P < 0.0001), SIRT2 (nonfrail – 15.18 ± 2.94 ng/μL; frail – 14.19 ± 2.66 ng/μL; P = 0.016), and SIRT3 (nonfrail-7.72 ± 1.84 ng/μL; frail – 6.12 ± 0.97 ng/μL; P < 0.0001) levels were significantly lower among frail patients compared with the nonfrail. In multivariable regression analysis, lower sirtuins level were significantly associated with frailty after adjusting age, gender, diabetes mellitus, hypertension, cognitive status (Mini Mental State Examination scores) and number of comorbidities. For detecting the optimum diagnostic cutoff value a ROC analysis was carried out. The area under curve for SIRT1 was 0.9037 (cutoff – 4.29 ng/μL; sensitivity – 81.48%; specificity – 79.83%) and SIRT3 was 0.7988 (cutoff – 6.61 ng/μL; sensitivity – 70.37%; specificity – 70.59%). This study shows that lower circulating SIRT1 and SIRT3 levels can be distinctive marker of frailty.
    Full-text · Article · Jul 2014 · Aging cell
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    • "Direct association between frailty and elevated circulating levels of interleukin (IL)-6, a proinflammatory cytokine, was first observed in community-dwelling older adults.22 A large number of studies in many cohorts of older adults and under various care settings have since provided evidence supporting the role of chronic inflammation and immune activation in the pathogenesis of the frailty syndrome.23–25 "
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    ABSTRACT: Frailty is a common and important geriatric syndrome characterized by age-associated declines in physiologic reserve and function across multiorgan systems, leading to increased vulnerability for adverse health outcomes. Two major frailty models have been described in the literature. The frailty phenotype defines frailty as a distinct clinical syndrome meeting three or more of five phenotypic criteria: weakness, slowness, low level of physical activity, self-reported exhaustion, and unintentional weight loss. The frailty index defines frailty as cumulative deficits identified in a comprehensive geriatric assessment. Significant progress has recently been made in understanding the pathogenesis of frailty. Chronic inflammation is likely a key pathophysiologic process that contributes to the frailty syndrome directly and indirectly through other intermediate physiologic systems, such as the musculoskeletal, endocrine, and hematologic systems. The complex multifactorial etiologies of frailty also include obesity and specific diseases. Major clinical applications include risk assessment and stratification. This can be applied to the elderly population in the community and in a variety of care settings. Frailty may also be useful for risk assessment in surgical patients and those with cardiovascular diseases, cancer, or human immunodeficiency virus infection, as well as for assessment of vaccine effectiveness in older adults. Currently, exercise and comprehensive geriatric interdisciplinary assessment and treatment are key interventions for frailty. As understanding of the biologic basis and complexity of frailty further improves, more effective and targeted interventional strategies and innovative geriatric-care models will likely be developed.
    Full-text · Article · Mar 2014 · Clinical Interventions in Aging
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