Age Differences in Eicosanoid Production of Mouse Splenocytes: Effects on Mitogen-induced T-cell Proliferation

Abstract

In order to determine the contribution of suppressive factors secreted front macrophages to the age-associated decline in T-cell mediated mitogenic responses, experiments were conducted to characterize eicosanoid and H₂O₂ production, total cellular fatty acid, and vitamin E composition of splenocytes isolated from young (4 mo) and old (24 mo) C57BLI 6NIA mice. An age-related increase was observed in CA⁺⁺ ionophore A23187-stimulated ex-vivo production of prostaglandin (PG) E₂, leukotriene (LT) B₄, and LTC⁴ (p < .01), and in concanavalin A (ConA)-stimulated PGE₂ 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 PGE₂ production was also observed in lipopolysacharide-stimulated peritoneal macrophages of C57BL/6N1A 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, PGE₂ 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 H₂O₂from splenocytes stimulated with 10 or 100 ng phorbol myristate acetate (PMA). These data indicate that aging is associated with increased production ofPG and LT from activated splenocytes. Inhibition of PGE₂ but not LT production enhances mitogenic responses of old mice, suggesting a contributory role for PGE₂ in the age-associated decline of T-cell responsiveness to polyclonal mitogens.