6th ESACP Congress, Heidelberg, April 7-11, 1999

A159
SIGNIFICANCE OF AN OVEREXPRESSION OF TNF FOR THE CYTOTOXIC NK ACTIVITY AND HEALTH STATUS OF THE ELDERLY
Mysliwski A, Mysliwska J, Bryl E

Department of Histology and Immunology, Medical University of Gdansk, Poland

The results of our earlier investigations suggested that the high production of TNF is associated with a low NK cytotoxic activity. In the present paper we wondered whether the inhibitory effect of an elevated level of TNF on NK activity in the elderly is realised by its suppressive action on the expression of the IL2Ralpha (CD25). Groups of volunteers (50 people each) aged 20-35 and 60-75 were enrolled into the study. The health was graded as healthy and non-fully healthy. The levels of TNF and Interleukin 2 (IL2) were measured in the sera and the supernatants of PBMC incubated with K562 cells for 4 h by bioassays. Cytotoxic NK activity was measured by a standard method with 51Cr. An expression of CD25 molecule was measured on CD16+ cells from resting and stimulated in vitro by TNF peripheral blood mononuclear cells (PBMC) and peripheral blood lymphocytes (PBL) by the flow cytometry. Our results revealed that the healthy people were characterised by a high NK activity while those non-fully healthy with a low NK response. An anti-TNF moAb suppressed the NK activity of the elderly low NK responders. Cells of the young people and the healthy elderly were characterised by a low secretion of TNF during NK cytotoxic reaction. At the same time a high amount of the bioactive TNF was released during the NK reaction of the non-fully healthy elderly. After 48 h of incubation with TNF in vitro, the increase in CD16+CD25+ (activated NK cells) was significantly higher in the group of the low NK responders. Our results suggest that the high production of TNF during NK reaction of the elderly low NK responders is necessary to maintain this response on the highest possible level through the generation of CD16+CD25+ cells.