Effects of tumor necrosis factor-alpha and interleukin-6 in elderly populations.

Aging is associated with low-grade increases in circulating levels of TNF-alpha and IL-6. A wide range of factors, including smoking, obesity, infections, the decline in sex hormones, and the genotype, induce and modify this age-related inflammatory activity, which on the other hand may cause age-related pathology. Several classical risk factors are indeed controlled by TNF-alpha and IL-6. TNF-alpha induces insulin resistance and endothelial dysfunction, IL-6 promotes procoagulant changes and both cytokines cause dyslipidaemia. Moreover, systemic low-grade elevations in both cytokines have been related to cardiovascular diseases and TNF-alpha has been associated with Alzheimer's disease and type 2 diabetes mellitus. TNF-alpha and IL-6 are also differently and independently of each other associated with mortality in elderly populations, indicating points of distinction in the biological effects of the two cytokines. Moreover, the association between cytokines and mortality is independent of co-morbidity, suggesting that low-grade increases in circulating cytokines are strong, independent risk factors of morbidity and mortality in old populations, although life style factors and co-morbidity may modulate levels.