Eicosanoids in rheumatoid arthritis.

Eicosanoids are potent mediators in the cellular microenvironment. Eicosanoids have different effects depending on tissue or organ, the polyunsaturated fatty acid content of the diet of the individual, and the net effect of local microenvironmental factors--as eicosanoids, cytokines, and hormones modulate each others' effects through a complex, multilevel network of interactions. In general, eicosanoids have significant net proinflammatory effects. In RA, the net proinflammatory effects of the prostanoids is underscored by the effectiveness of the cyclooxygenase antagonists (NSAIDs), and recent data indicate a proinflammatory effect of the leukotrienes. Changes in the dietary polyunsaturated fatty acid composition to increased intake of marine n-3 fatty acids and/or dihomogamma-linolenic acid may favorably modulate eicosanoid synthesis towards less inflammatory or antiinflammatory eicosanoids and may ameliorate disease activity in RA. Recent advances in the biochemistry and molecular biology of the eicosanoid receptors and the synthetic pathways of eicosanoids will provide opportunities for advances in the therapeutics for RA, including selective cyclooxygenase (PGHS-2) antagonists, selective eicosanoid receptor antagonists and agonists, and selective inhibitors of PGH2 isomerases and enzymes of the 5-lipoxygenase pathway.