DYSREGULATION OF IL-10 PRODUCTION WITH AGING - POSSIBLE LINKAGE TO THE AGE-ASSOCIATED DECLINE IN DHEA AND ITS SULFATED DERIVATIVE

Peripheral lymphoid cells isolated from the spleens and peritoneal cav ities of aged mice were found to constitutively secrete the multifunct ional cytokine interleukin (IL)-10 when cultured in vitro. B-Lymphocyt es were implicated as the cell type responsible. Abnormal expression o f this cytokine was also detected in vivo because high levels of mRNA for IL-10 were present in splenocytes freshly isolated from aged anima ls, In addition to the spontaneous secretion of IL-10, lymphoid cells from aged donors were hyperresponsive to exogenous stimulation with en dotoxin, producing exaggerated quantities of both IL-10 and IL-6 in cu lture. Treatment of aged animals with dehydroepiandrosterone sulfate ( DHEAS), a natural steroid, reversed the age-associated alterations in cytokine production, rendering the treated mice quite similar to matur e adult controls. DHEAS treatment of aged mice also resulted in a lowe ring in the number of B1 cells present in the peritoneal cavity and al so reduced the titers of circulating autoantibodies specific for phosp hatidylcholine (PtC), Based on its wide range of biologic activities, a dysregulation in the mechanisms that control IL-10 production could be a major contributor to immunosenescence. The ability of DHEAS treat ment to restore normal control over the expression of IL-10 may explai n how this steroid enhances immunocompetence in aged animals.