AGE-DIFFERENCES IN EICOSANOID PRODUCTION OF MOUSE SPLENOCYTES - EFFECTS ON MITOGEN-INDUCED T-CELL PROLIFERATION

In order to determine the contribution of suppressive factors secreted from macrophages to the age-associated decline in T-cell mediated mitogenic responses, experiments were conducted to characterize eicosanoid and H2O2 production, total cellular fatly acid, and vitamin E composition of splenocytes isolated from young (4 mo) and old (24 mo) C57BL/6NIA mice. An age-related increase was observed in Ca++ ionophore A23187-stimulated ex-vivo production,of prostaglandin (PG) E(2), leukotriene (LT) B-4, and LTC(4) (p < .01), and in concanavalin A (ConA)-stimulated PGE(2) production (p < .01). No age-related difference was observed in ex-vivo production of 12- and 15- hydroxyeicosatetranoic acid (HETE). The age-related increase in PGE(2) Production was also observed in lipopolysacharide-stimulated peritoneal macrophages of C57BL/6NIA mice and ConA and phytohemagglutinin (PHA)-stimulated splenocytes isolated from DBA mice. Inhibition of cyclooxygenase with indomethacin resulted in increased ConA-stimulated proliferation of splenocytes from old mice (p < .01), while 5-lipoxygenase inhibition did not have an effect on mitogen induced proliferation. Furthermore, PGE(2) addition to purified splenic T-cells decreased their proliferation. No age-related differences were observed in total cellular fatty acid composition, vitamin E level, or ex-vivo production of H2O2 from splenocytes stimulated with 10 or 100 ng phorbol myristate acetate(PIMA). These data indicate that aging is associated with increased production of PG and LT from activated splenocytes. Inhibition of PGE(2) but not LT production enhances mitogenic responses of aid mice, suggesting a contributory role for PGE(2) in the age-associated decline bf T-cell responsiveness to polyclonal mitogens.