INCREASED CYTOKINE PRODUCTION IN MONONUCLEAR-CELLS OF HEALTHY ELDERLYPEOPLE

The production of cytokines during aging, except interleukin (IL)-2, h as been neglected in humans.We measured the in vitro production of IL- 6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and IL-1b eta by peripheral mononuclear cells from selected healthy young (mean age 26.8 years) and aged (mean age 80.2 years) subjects. Significant i ncreases of IL-6, TNF-alpha and IL-1beta levels were found in mitogen- stimulated cultures from aged donors, occurring at 24 to 72 h after st imulation. No significant differences were observed for IFN-gamma prod uction. Proliferative capability of cells stimulated with PHA was not impaired in aged subjects. Since the amounts of all cytokines studied were similar in unstimulated cultures from young and aged subjects, an d also serum levels of TNF-alpha did not differ, these data indicate t hat the cellular machinery for the production of these cytokines is we ll preserved in aging, and also that cells from old people are able to up-regulate their production in response to appropriate stimuli. The increases in cytokine synthesis were not dependent on changes in the n umber of monocytes, nor were they related to the significant rise of C D45RO+, and the concomitant decrease of CD45RA+, occurring in both CD4 + and CD8+ lymphocytes from aged subjects. The increased production of pro-inflammatory cytokines by stimulated mononuclear cells of healthy aged subjects may be relevant to several aspects of age-associated pa thological events, including atherosclerosis, osteoporosis, fibrosis a nd dementia.