Influence of age on the production and regulation of interleukin-1 in mice

The decrease in T-cell proliferation with age is due, in part, to the decline in the production of IL-2. Since IL-1 is needed to trigger IL-2 production, we determined the IL-1 producing capacity of peritoneal macrophages of young (2-4 months) and old (24-26 months) BALB/c and C57BL/6 mice. Mice were stimulated with LPS, and their peritoneal macrophages were obtained 3 days later, purified, and assessed for IL-1 production by coculturing them with splenic T cells at a ratio of 1:5 in the presence of LPS. Supernatants were obtained 4 days later when the PGE2 and IL-2 activities were minimal and IL-1 activity maximal. IL-1 activity was assessed for their ability to augment the proliferative activity of indicator thymocytes in their response to PHA stimulation. The results revealed that (i) IL-1 production by cells of old BALB/c and C57BL/6 mice is reduced to about 40% and 30% that of young mice, respectively; (ii) indomethacin enhances IL-1 production by cells of both young and old mice to the same extent; and (iii) reduction in the IL-1 producing capacity by cells of old mice results from altered activities of both the IL-1 producing peritoneal macrophages and the augmenting T cells.