SEX AND PARITY MODULATE CYTOKINE PRODUCTION DURING MURINE AGING

We have previously shown that physiological hormone differences relate d to pregnancy or sex affect the age-related distribution of mononucle ar cell populations during murine ageing. To determine whether such ch anges are involved in the age-related changes in functions of T cells, we examined the secretion of major T cell immunoregulatory cytokines (IL-2, IL-4, interferon-gamma (IFN-gamma), IL-3, IL-6 and granulocyte- macrophage colony-stimulating factor (GM-CSF)) of in vitro concanavali n A-activated spleen cells of C57B1/6 mice. The study included multipa rous and virgin females and males at 2, 8, 15 and 23 months of age. Sh ort-term effects of parity (8 months) were evidenced by the decrease o f IFN-gamma and the preserved IL-2 production in multiparous females ( 8 months), while IFN-gamma was unchanged and IL-2 decreased in virgin mice. The increase in IL-4 production appeared earlier in multiparous females (15 months) than in virgin mice (23 months). The increase in I L-4/IFN-gamma and IL-4/IL-2 ratios at 8 and 15 months, respectively, i n multiparous females, suggests that pregnancy modifies the Th1/Th2 eq uilibrium. In late adulthood (15 months), IL-6 and GM-CSF production w as higher in multiparous females than in virgin males or females. Sex differences were also noticed: IFN-gamma secretion capacity was lower in males than in females during ageing. This study underlines that the onset, magnitude and kinetics of the age-related changes in cytokine production are parity-and sex-dependent. These changes probably influe nce the incidence of age-related diseases and may explain the greater longevity of females.