Eicosanoids, inflammation, and anti-inflammatory drugs.
Many mediators of inflammation are derived from arachidonic acid including prostaglandins, leukotrienes, and other oxygenated derivatives. In addition, platelet activating factor is an acetylated ether-linked phospholipid formed by cleaving arachidonic acid from phospholipid precursors. Several of these mediators produce vasodilation and increased vascular permeability either alone or acting synergistically with other mediators. The E prostaglandins also stimulate bone resorption and activate adenylate cyclase, and leukotriene B4 is chemotactic and activates leukocytes. Both B and T cell functions are inhibited by PGE2 and some lipoxygenase products alter T cell function as well. Prostaglandin and leukotriene synthesis are closely regulated; they are stimulated by a number of activators, hormones, cytokines, and growth factors. The major therapeutic as well as toxic effects of NSAIDs are accounted for by inhibition of cyclooxygenase activity and, therefore, prostaglandin synthesis. The NSAIDs do not inhibit leukotriene synthesis, and under some conditions these drugs may augment the production of leukotrienes. Synthesis of both prostaglandins and leukotrienes are inhibited by glucocorticoids through lipomodulin-mediated inhibition of arachidonic acid release. Nutritional regulation of prostaglandin and leukotriene production may occur by substitution of alternative dietary polyunsaturated fatty acids such as the n-3 fatty acids present in marine lipids. New drugs which inhibit the synthesis of leukotrienes and platelet activating factor may be useful therapeutic agents.
Robinson
D R
DR
Department of Medicine, Massachusetts General Hospital, Boston.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015777:Eicosanoids / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology*; D015289:Leukotrienes / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology; D010972:Platelet Activating Factor / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D013931:Thromboxanes / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D015289:Leukotrienes; D010972:Platelet Activating Factor; D011453:Prostaglandins; D013931:Thromboxanes