Suppression of Murine T-Cell Mitogenesis by Metabolic Products of Arachidonic Acid

Abstract

We examined the ability of arachidonic acid (AA) to inhibit mitogen stimulation of mouse splenic lymphocytes. Dose related suppression of [3H]-thymidine incorporation by cells stimulated with either phytohemagglutinin or concanavalin A occurred at concentrations of AA above lµg/ml. AA-induced suppression required that AA be added to cultures within 6 hours of the addition of mitogen. Addition of AA at 24 hours resulted in diminished suppression, while delaying addition of AA until 48 hours had no effect on mitogen stimulation. Preincubation with AA did not alter mitogen stimulation when cells were washed free of AA. The addition of indomethacin or mefanamic acid to the cultures significantly reversed AA-induced suppression. Inhibitors of the lipoxygenase pathway or thromboxane synthesis had no effect, while an inhibitor of both thromboxane and prostacyclin synthesis partially prevented AA-induced suppression only at the highest concentration of AA. Removal of adherent cells resulted in a diminished capacity for AA to suppress mitogenesis and to stimulate PGE₂ synthesis.