Arachidonic acid metabolites: mediators of inflammation in asthma.
Asthma is increasingly recognized as a mediator-driven inflammatory process in the lungs. The leukotrienes (LTs) and prostaglandins (PGs), two families of proinflammatory mediators arising via arachidonic acid metabolism, have been implicated in the inflammatory cascade that occurs in asthmatic airways. The PG pathway normally maintains a balance in the airways; both PGD2 and thromboxane A2 are bronchoconstrictors, whereas PGE2 and prostacyclin are bronchoprotective. The actions of the LTs, however, appear to be exclusively proinflammatory in nature. The dihydroxy-LT, LTB4, may play an important role in attracting neutrophils and eosinophils into the airways, whereas the sulfidopeptide leukotrienes (LTC4, LTD4, and LTE4) produce effects that are characteristic of asthma, such as potent bronchoconstriction, increased endothelial membrane permeability leading to airway edema, and enhanced secretion of thick, viscous mucus. Given the significant role of the inflammatory process in asthma, newer pharmacologic agents, such as the sulfidopeptide-LT antagonists, zafirlukast, montelukast, and pranlukast and the 5-lipoxygenase (5-LO) inhibitor, zileuton, have been developed with the goal of targeting specific elements of the inflammatory cascade. These drugs appear to represent improvements to the existing therapeutic armamentarium. In addition, the results of clinical trials with these agents have helped to expand our understanding of the pathogenesis of asthma.
Wenzel
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National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206-1900, USA.
D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology; D016718:Arachidonic Acid / Q000378:metabolism*; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D015289:Leukotrienes / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins / Q000378:metabolism
D018836:Inflammation Mediators; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase