AGE-RELATED ENHANCEMENT OF TUMOR-NECROSIS-FACTOR (TNF) PRODUCTION IN MICE

We investigated age-related changes in the production of TNF at the ce llular level using immunocompetent peritoneal and spleen cells from C3 H/He mice of various ages. The density of cultured peritoneal macropha ges and spleen cells required for TNF production was at least 5 x 10(5 ) cells/dish. The optimal concentration of OK-432 for 24-h culture of peritoneal macrophages (1 x 10(6) cells) and spleen cells (1 x 10(7) c ells) was 0.5 and 0.1 KE/ml, respectively. Among peritoneal cells, adh erent macrophages were the major TNF-producing cells, whilst nonadhere nt T or B cells alone did not produce TNF after stimulation with OK-43 2. In the case of spleen cells, T or B cells were involved in the prod uction of TNF when cultured with a few adherent cells in the presence of OK-432. However, T or B cells alone failed to produce TNF, Producti on of TNF by peritoneal macrophages from both male and female mice inc reased significantly with aging. In contrast, although TNF production by spleen cells tended to increase with aging, no significant change w as noted. The total number of peritoneal and spleen cells: respectivel y increased up to about 18 months after birth with B cells being princ ipally responsible for this age-related increase. We previously report ed that systemic production of TNF increases with aging. The present s tudy of TNF production at the cellular level in mice indicated (1) tha t TNF production per macrophage increased with aging, and (2) that the number of T and B cells involved in the production of TNF in the pres ence of macrophages also increased at least up to middle age.