Effect of orally administered eicosapentaenoic acid (EPA) on the formation of leukotriene B 4 and leukotriene B 5 by rat leukocytes

Abstract

Eicosapentaenoic acid (EPA) is a poor substrate for the fatty acid cyclo-oxygenase but is a good substrate for lipoxygenase enzymes which catalyse the biosynthesis of hydroperoxy-acids, hydroxy-acids and leukotrienes. Recently, we reported that leukotriene B 5 (LTB 5) was at least 30 times less potent than LTB 4 in causing aggregation, chemokinesis and degranulation of polymorphonuclear leukocytes in vitro. In this paper, the effect of oral administration of EPA on LTB 4 and LTB 5 production by rat leukocytes stimulated with the calcium ionophore, A23187, was assessed. The concentration of LTB was determined by radioimmunoassay and also by reverse-phase high pressure liquid chromatography using PGB 3 as internal standard. Supplementation of a normal rat diet with EPA (240 mg/kg per day) for 4 weeks caused a significant increase in the formation of LTB 5 and a decrease in the synthesis of LTB 4 by stimulated leukocytes. The EPA-rich diet significantly increased the EPA content of leukocyte phospholipids without altering the content of arachidonic acid (AA) or linoleic acid. The ratio of EPA/AA in leukocytes correlated (r = 0.795, P < 0.001) with the LTB 5/LTB 4 ratio produced after stimulation of leukocytes. If LTB 4 has a chemotactic role during inflammation, the present data suggest that an EPA rich diet could decrease the accumulation of leukocytes at sites of inflammation.