Interleukin-1 synthesis and activity in aged mice.

Recent studies have provided evidence that deficient interleukin-2 (IL-2) production by helper T cells contributes to the impaired T-cell-mediated functions observed in aged mice. Since most of these responses depend upon the presence of macrophages, a deficit in the functional capacity or in cell cooperation of macrophages may result in a decrease in immune reactivity. We found in the present study, that in vitro the cytostatic activity of macrophages from aged C57BL/6 (B6) mice is affected only slightly, but that in vivo their number increases with age. The synthesis of IL-1 is reduced when macrophages from aged mice are stimulated in vitro by lipopolysaccharide, but addition of exogenous IL-1 apparently does not restore either the mixed lymphocyte reaction or cytotoxic T lymphocyte generation. Co-cultures of young splenic macrophages with aged T lymphocytes do not restore to normal level the impaired proliferative response to T mitogens of aged B6 mice, but aged splenic macrophages provide a full accessory help for mitogenesis of young T cells. Thus, absorption of IL-1 by phytohemagglutinin-activated T cells is slightly altered in aged mice. IL-2 responsive T cells are not altered since exogenous IL-2 supply in vitro completely reconstitutes cytotoxic T lymphocyte generation after an allogeneic stimulation. Moreover, the number of Lyt 1+ cells is not modified in aged B6 mice. These results suggest that the impaired capacity of macrophages to release IL-1 and of blast T cells to bind IL-1 may contribute to the depression of cell-mediated immune reactivity associated with aging but also that the main defect is a functional lesion of IL-2 production by Lyt 1+ helper T cells.