Robinson D R
Department of Medicine, Massachusetts General Hospital, Boston.
Clin Exp Rheumatol. 1989 Sep-Oct;7 Suppl 3:S155-61.
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.
许多炎症介质来源于花生四烯酸，包括前列腺素、白三烯及其他氧化衍生物。此外，血小板活化因子是一种通过从磷脂前体中裂解花生四烯酸形成的乙酰化醚连接磷脂。这些介质中的几种单独或与其他介质协同作用，可产生血管舒张和增加血管通透性。E 型前列腺素还刺激骨吸收并激活腺苷酸环化酶，白三烯 B4 具有趋化作用并激活白细胞。PGE2 抑制 B 细胞和 T 细胞功能，一些脂氧合酶产物也会改变 T 细胞功能。前列腺素和白三烯的合成受到严格调控；它们受到多种激活剂、激素、细胞因子和生长因子的刺激。非甾体抗炎药的主要治疗作用和毒性作用是通过抑制环氧化酶活性，从而抑制前列腺素合成来实现的。非甾体抗炎药不抑制白三烯合成，在某些情况下，这些药物可能会增加白三烯的产生。糖皮质激素通过脂调蛋白介导的花生四烯酸释放抑制作用，抑制前列腺素和白三烯的合成。通过替代膳食中的多不饱和脂肪酸，如海洋脂质中存在的 n-3 脂肪酸，可能会对前列腺素和白三烯的产生进行营养调控。抑制白三烯和血小板活化因子合成的新药可能是有用的治疗药物。
