AN ANTIBODY SPECIFIC FOR INTERLEUKIN-6 REVERSES AGE-ASSOCIATED CHANGES IN SPONTANEOUS AND INDUCED CYTOKINE PRODUCTION IN MICE

A number of quantitative and qualitative changes in the pattern of cyt okine production have been reported to accompany the process of ageing in laboratory animals and in human populations, including an increase in serum levels of interleukin-1 (IL-1) and IL-6, as well as increase d concanavalin A (ConA)-stimulated production of IL-4, IL-10 and trans forming growth factor-beta (TGF-beta), and decreased production of IL- 2 from cultured spleen cells. Increased IL-1 and IL-6 production is a feature of splenic adherent cells and peritoneal exudate cells taken f rom aged mice and stimulated with lipopolysaccharide in vitro. We have asked whether the altered production of lymphocyte-derived cytokines (IL-4, IL-2, TGF-beta) is itself a function of a primary alteration in IL-1/IL-6 production (from macrophage/monocytes) by infusing monoclon al antibodies to these cytokines prior to harvesting cells from aged m ice and stimulating the cells in vitro. Anti-IL-6, but not anti-IL-1, reversed the age-associated alteration in lymphocyte cytokine producti on. The general pattern of cytokine production in aged mice is of a ty pe-2 cytokine type, and thus these data are consistent with the idea t hat increased production of IL-6 in aged animals is causally implicate d in this age-associated polarization to type-2 cytokine production.