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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 proinflammatory cytokines-tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL6) in the absence of the inflammatory stimulus, a phenomenon 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 cells. We measured the levels of bioactive TNF alpha and IL6 during cytotoxic NK reactions and analyzed the effect of neutralizing monoclonal antibodies anti-TNF alpha and anti-IL6 on the outcome of cytotoxic reaction. Bioactive TNF alpha was produced in higher amounts during cytotoxic reactions of the elderly with low NK activity in comparison with its production by the elderly with high NK activity. Anti-TNF alpha decreased already low cytotoxic responses of the elderly while not having an effect on the cytotoxic potential of high responders. More of the bioactive IL6 was released during cytotoxic reactions of the elderly as compared with young people. There was, however, no relation between the height of NK cytotoxic activity and the amount of IL6. Our results suggest that the increased level of TNF alpha seen in the elderly low NK responders may pose a compensatory mechanism, necessary to keep the highest possible level of NK responses. The increased bioactivity of IL6 during NK reaction of the elderly does not seem to participate in the regulation of the level of NK cytotoxic activity.