OVERACTIVITY OF TUMOR-NECROSIS-FACTOR-ALPHA BUT NOT INTERLEUKIN-6 IS ASSOCIATED WITH LOW NATURAL-KILLER CYTOTOXIC ACTIVITY IN THE ELDERLY

In this paper we asked whether the increased production of two proinfl ammatory cytokines - tumor necrosis factor-alpha (TNF alpha) and inter leukin-6 (IL6) in the absence of the inflammatory stimulus, a phenomen on frequently occurring in the elderly, may contribute to the decrease of natural killer (NK) cytotoxic activity. NK cell activity is a part of a nonspecific immunity directed against infected and transformed c ells. Wie measured the levels of bioactive TNF alpha and IL6 during cy totoxic NK reactions:and analyzed the effect of neutralizing monoclona l antibodies anti-TNF alpha and anti-IL6 on the outcome of cytotoxic r eaction. Bioactive TNF alpha was produced in higher amounts during cyt otoxic reactions of the elderly with low NK activity in comparison wit h its production by the elderly with high NK activity, Anti-TNF alpha decreased already low cytotoxic responses of the elderly while not hav ing an effect on the cytotoxics potential of high responders. More of the bioactive IL6 was released during cytotoxic reactions of the elder ly as compared with young people. There was, however, no relation betw een the height of NK cytotoxic activity and the amount of IL6. Our res ults suggest that the Increased level of TNF alpha seen in the elderly low NK responders may pose a compensatory mechanism, necessary ro kee p the highest possible level of NK responses. The increased bioactivit y of IL6 during NK reaction of the elderly does not seem to participat e In the regulation of the level of NK cytotoxic activity.