Long-chain polyunsaturated fatty acids and inflammation

Abstract

Although part of the normal host response to infection or injury, inflammation is involved in many pathological conditions and disease states. Most interest in the influence of fatty acids on inflammatory processes has centred on the opposing actions of n-6 and n-3 polyunsaturated fatty acids (PUFAs). The n-6 PUFA arachidonic acid gives rise to the eicosanoid family of inflammatory mediators (prostaglandins, leukotrienes and related metabolites) and through these regulates the activities of inflammatory cells, the production of inflammatory cytokines, etc. Consumption of long-chain n-3 PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] decreases the amount of arachidonic acid in inflammatory cell membranes and so available for eicosanoid production. Thus, consumption of long-chain n-3 PUFAs results in decreased production of eicosanoids from arachidonic acid. EPA acts as an alternative substrate for eicosanoid synthesis giving rise to mediators tha t are less potent than the analogues produced from arachidonic acid. EPA and DHA give rise to newly discovered families of mediators termed E- and Dresolvins, respectively, which have anti-inflammatory and inflammation-resolving actions. In addition to this range of effects, long-chain n-3 PUFAs affect cell-signalling processes and gene expression in inflammatory cells, resulting in decreased expression of inflammatory cytokines and adhesion molecules. Such long-chain n-3 PUFA-induced effects may be of importance in protecting against the development of and lowering the severity of acute and chronic inflammatory conditions. There is good evidence for the efficacy of long-chain n-3 PUFAs in rheumatoid arthritis, with less strong evidence in other inflammatory conditions. The precursor n-3 PUFA, ?-linolenic acid, exerts some anti-inflammatory effects at very high intakes, perhaps reflecting the need for its conversion to EPA to be effective. Keywords: arachidonic acid; cytoki n e; eicosanoid; fish oil; inflammation; macrophage