Eicosapentaenoic acid as a modulator of inflammation: Effect on prostaglandin and leukotriene synthesis

Abstract

Products derived from arachidonic acid (AA) via both the cyclo-oxygenase and lipoxygenase pathways play a role in inflammation: prostaglandins (PGs), particularly PGE 2, contribute to the formation of oedema, erythema and hyperalgesia whereas leukotriene B 4 (LTB 4), a product of the 5′ lipoxygenase, may modulate the recruitment of leukocytes. We have previously reported that supplementation of a standard rat diet with eicosapentaenoic acid (EPA) caused a significant increase in the formation of LTB 5, which is less active biologically than LTB 4, and a decrease in the synthesis of LTB 4 by stimulated leukocytes. Now we have assessed the effects of administration of highly purified EPA ethyl ester (79% pure), in two models of acute inflammation. Supplementation of a standard rat diet with 240 mg/kg/day EPA for 4 weeks significantly decreased the concentration of PGE 2 and TXB 2 in inflammatory exudate derived from implantation of carrageenin impregnated sponges: neither the concentration of LTB 4 nor the cell number were reduced significantly. Triene prostaglandins were not detected in the exudate, however, significant levels of LTB 5 were present. In the second model, oedema induced by injection of carrageenin into rat paws was significantly reduced in animals fed an EPA-rich diet. Supplementation of the diet with EPA could, by mainly reducing the synthesis of prostaglandins, offer a novel and non-toxic approach to the modulation of an inflammatory response.