Leukotrienes: Mediators of Immediate Hypersensitivity Reactions and Inflammation

Arachidonic acid plays a central role in a biological control system where such oxygenated derivatives as prostaglandins, thromboxanes, and leukotrienes are mediators. The leukotrienes are formed by transformation of arachidonic acid into an unstable epoxide intermediate, leukotriene A 4 , which can be converted enzymatically by hydration to leukotriene B 4 , and by addition of glutathione to leukotriene C 4 . This last compound is metabolized to leukotrienes D 4 and E 4 by successive elimination of a γ-glutamyl residue and glycine. Slow-reacting substance of anaphylaxis consists of leukotrienes C 4 , D 4 , and E 4 . The cysteinyl-containing leukotrienes are potent bronchoconstrictors, increase vascular permeability in postcapillary venules, and stimulate mucus secretion. Leukotriene B 4 causes adhesion and chemotactic movement of leukocytes and stimulates aggregation, enzyme release, and generation of superoxide in neutrophils. Leukotrienes C 4 , D 4 , and E 4 , which are released from the lung tissue of asthmatic subjects exposed to specific allergens, seem to play a pathophysiological role in immediate hypersensitivity reactions. These leukotrienes, as well as leukotriene B 4 , have pro-inflammatory effects.