Ogawa Yoshiko, Calhoun William J
Division of Allergy, Pulmonary, Immunology, Critical Care, and Sleep (APICS), University of Texas Medical Branch, TX 77555-0561, USA.
J Allergy Clin Immunol. 2006 Oct;118(4):789-98; quiz 799-800. doi: 10.1016/j.jaci.2006.08.009.
Cysteinyl leukotrienes (cysLTs) are a class of closely structurally related lipid molecules, originally described as slow-reacting substance of anaphylaxis, with a myriad of biologic functions. These activities include producing smooth muscle contraction and mucus secretion, recruiting allergic inflammatory cells, modulating cytokine production, influencing neural transmission, and altering structural changes in the airway. Administration of cysLTs to animals and human subjects reproduces many features of allergic inflammation and asthma. Leukotriene (LT) blockers have independent efficacy in asthma and improve pulmonary function when added to inhaled steroids. Conversely, blockade of this pathway both in animals and in human subjects results in important reductions in inflammation and its consequences and might reduce structural changes of remodeling. These data collectively make a compelling case for an important role of cysLTs in airway inflammation and asthma. However, the magnitude of effect of anti-LTs is smaller than that of corticosteroids, and there is more variability in benefit of LT blockade than is seen with inhaled steroids. In addition, adding anti-LTs to inhaled steroids in asthmatic patients does not appear to produce added anti-inflammatory benefit. Genetic polymorphisms and environmental factors, such as tobacco smoke exposure, might underlie some of the heterogeneity of response to LT blockers.
半胱氨酰白三烯（cysLTs）是一类结构紧密相关的脂质分子，最初被描述为过敏反应迟缓物质，具有多种生物学功能。这些活性包括引起平滑肌收缩和黏液分泌、募集过敏性炎症细胞、调节细胞因子产生、影响神经传递以及改变气道结构变化。给动物和人类受试者施用半胱氨酰白三烯可重现过敏性炎症和哮喘的许多特征。白三烯（LT）阻滞剂在哮喘中具有独立疗效，与吸入性类固醇联合使用时可改善肺功能。相反，在动物和人类受试者中阻断该途径会导致炎症及其后果显著减轻，并可能减少重塑的结构变化。这些数据共同有力地证明了半胱氨酰白三烯在气道炎症和哮喘中起重要作用。然而，抗白三烯药物的作用强度小于皮质类固醇，并且白三烯阻断的益处比吸入性类固醇的变异性更大。此外，在哮喘患者中，将抗白三烯药物与吸入性类固醇联合使用似乎不会产生额外的抗炎益处。遗传多态性和环境因素，如接触烟草烟雾，可能是对白三烯阻滞剂反应异质性的部分原因。
