Wenzel S E
National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206-1900, USA.
Pharmacotherapy. 1997 Jan-Feb;17(1 Pt 2):3S-12S.
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.
哮喘越来越被认为是肺部由介质驱动的炎症过程。白三烯（LTs）和前列腺素（PGs）是通过花生四烯酸代谢产生的两类促炎介质，它们参与了哮喘气道中发生的炎症级联反应。PG途径通常维持气道的平衡；PGD2和血栓素A2都是支气管收缩剂，而PGE2和前列环素具有支气管保护作用。然而，LTs的作用本质上似乎完全是促炎的。二羟基-LT，即LTB4，可能在吸引中性粒细胞和嗜酸性粒细胞进入气道方面起重要作用，而硫肽白三烯（LTC4、LTD4和LTE4）产生哮喘特有的效应，如强效支气管收缩、导致气道水肿的内皮膜通透性增加以及浓稠黏液分泌增强。鉴于炎症过程在哮喘中的重要作用，已开发出新型药物制剂，如硫肽-LT拮抗剂扎鲁司特、孟鲁司特和普仑司特以及5-脂氧合酶（5-LO）抑制剂齐留通，目标是针对炎症级联反应的特定环节。这些药物似乎是对现有治疗药物的改进。此外，这些药物的临床试验结果有助于扩展我们对哮喘发病机制的理解。
