Compensatory effect of TNF alpha on low natural killer activity in the elderly

Regulatory effect of CD25, an activation antigen the alpha subunit of inter leukin 2 receptor (IL2R) on the activity of natural killer (NK) cells was s tudied in fifty elderly (57-70 years old) and fifty young people (19-35 yea rs old). Cytotoxic NK activity was assessed by Cr-51 release assay, the lev els of interleukin 2 (IL2) and tumour necrosis factors alpha (TNF alpha) we re measured using bioassays and expression of CD16 and CD25 proteins by flo w cytometry. Low MK activity in the elderly was associated with decline of full health, lowered serum concentration of IL2 and increased production of TNF alpha during ME reaction. Inhibition of TNF alpha activity by anti-TNF monoclonal antibody suppressed exclusively MK activity of low ME responder s. Moreover, stimulation in vitro of blood mononuclear cells, with TNF alph a induced in the elderly low NK responders a significantly higher increase of the CD25 expression on the surface of NK cells as compared with that in the elderly high responders. Since the CD25 molecule constitutes a subunit of the high affinity receptor, binding IL2 to immunocompetent cells, its in creased expression on MZ cells of low NK responders would enable them to bi nd even low amounts of the: endogenous IL2 available in this group of the e lderly. Thus, an overproduction of TNF alpha seems to be a mechanism compen sating, in the non-fully healthy elderly, for the decreased IL2 production, promoting efficient cytotoxic reaction.