MACROPHAGE PROSTAGLANDIN PRODUCTION CONTRIBUTES TO THE AGE-ASSOCIATEDDECREASE IN T-CELL FUNCTION WHICH IS REVERSED BY THE DIETARY ANTIOXIDANT VITAMIN-E

The aging process is associated with a decline in T cell-mediated immu nity, including decreased interleukin (IL)-2 production and mitogen-in duced T cell proliferation. Because macrophages (M phi) from old mice have higher production of prostaglandin (PG) E(2) than young mice, and PGE(2) has been shown to suppress T cell-mediated function, we hypoth esized that increased production of PGE(2) would contribute to decreas ed T cell function with aging and that decrease in PGE(2) production b y dietary antioxidants would enhance T cell-mediated function. Experim ents were conducted in which combinations of purified M phi and T cell s (> 95% pure) from young or old C57BL/6NIA mice were cultured togethe r. Go-cultures containing T cells and M phi from old mice had reduced ConA-stimulated proliferation and IL-2 secretion than those consisting of T cells and M phi from young mice. Addition of M phi from old mice suppressed proliferation and IL-2 secretion by T cells from young mic e. Likewise, T cells from old mice secreted more IL-2 when cultured wi th M phi from young mice compared to those cultured with M phi from ol d mice. Addition of PGE(2), at concentrations produced by old M phi, d ecreased proliferation and IL-2 production by young but not old T cell s. Neither addition of H2O2 at physiological levels, nor catalase chan ged the response of cultures from young or old mice. However, addition of indomethacin and the antioxidant nutrient vitamin E, both of which decreased PGE(2) production, improved T cell proliferation and IL-2 p roduction. These experiments demonstrate that increased production of PGE(2) by M phi contributes to the age-associated decline in T cell fu nction. Vitamin E improves T cell responsiveness in old mice mostly by reducing M phi PGE(2) production, although a direct effect of vitamin E on T cells was also observed. (C) 1997 Elsevier Science Ireland Ltd .