Age-related inflammatory cytokines and disease
Section snippets
Pro- and anti-inflammatory cytokines
Most information about cytokines comes from studies on acute infections and tissue injury. Pro- and anti-inflammatory cytokines are considered to be a highly dynamic part of the inflammatory response. Cytokines are released at the site of inflammation (caused by an infectious pathogen or traumatic injury) and facilitate an influx of lymphocytes, neutrophils, monocytes, and other cells that participate in the clearance of the antigen and healing. The local inflammatory response is accompanied by
Aging and the acute-phase response
It commonly is believed that aging is associated with a poor fever response and leukocyte response to infections. Clinical studies of acute serious illness have indicated that older individuals are less prone to develop fever and leucocytosis and are more susceptible to die from infections than are younger individuals [8], [9], [10]. It is not clear if underlying severe disease or aging is the cause of the impaired inflammatory responses.
In vitro stimulations of isolated PMNCs and whole blood
Chronic elevations of levels of circulating cytokines in the elderly
Increased plasma levels of TNF-α, IL-6, and sTNFR [33], [34], [35], [36], [37], [38] consistently have been demonstrated in elderly cohorts. Older individuals have also elevated concentrations of acute-phase proteins, such as CRP and serum amyloid A [39], and high neutrophil counts [11]. Plasma levels of TNF-α were correlated with production of IL-6, sTNFR, and CRP in centenarians [33], indicating an interrelated activation of the entire inflammatory cascade. Most immunogerontologic studies
Cytokines and chronic diseases in the elderly
Inflammatory activity is a characteristic part of the pathologic processes in several age-associated disorders, including atherosclerosis [82], heart failure [83], type 2 DM [84], sarcopenia [85], osteoporosis [86], AD [87], and Parkinson's disease [88]. This finding suggests that chronic low-grade elevations in circulating levels of cytokines are related to chronic diseases in cohorts of older individuals. The authors focus on AD, atherosclerotic cardiovascular diseases (CVDs), and type 2 DM,
Cytokines and mortality in the elderly
One major problem in epidemiologic cross-sectional studies is that it cannot be determined whether low-grade inflammatory activity is a causative factor of age-related disease or is a result of general immune activation caused by underlying pathologic processes. Longitudinal studies, such as mortality studies, may prove useful in studying this aspect. Although TNF-α is an important originator of the inflammatory cascade, few studies have evaluated the effect of low-grade elevations in TNF-α
Cytokine response to exercise
It has been well demonstrated that the plasma concentration of IL-6 increases during exercise, even during low-intensity exercise [143], [144]. This increase is followed by the appearance of cytokine inhibitors, such as IL-1 receptor antagonist, sTNFRs, and the anti-inflammatory cytokine IL-10 [145], [146], [147]
Concentrations of the chemokines IL-8, MIP-1α, and MIP-1β are elevated after strenuous exercise [148]. Most exercise studies, however, show no effect of exercise on the production of
Summary
Aging is associated with chronic low-grade increases in circulating levels of inflammatory markers. A wide range of environmental factors, including smoking, infections, and obesity, genetic factors, and the declining function of sex hormones may contribute to systemic low-grade inflammatory activity in older individuals. Age-associated disease may exacerbate this phenomenon. The multifunctional cytokines TNF-α and IL-6 have been associated with morbidity and mortality in the elderly. Evidence
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