Antileukotriene Agents for the Treatment of Lung Disease
Antileukotriene Agents for the Treatment of Lung Disease
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DOI：
10.1164/rccm.201301-0023pp
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发表时间：
2013-09-01
影响因子：
24.7
通讯作者：
Peters-Golden, Marc
中科院分区：
文献类型：
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作者：
Scott, Jacob P.;Peters-Golden, Marc
白三烯(Lts)C4、D4和E4统称为半胱氨酰白三烯(cysteinyl Lts，CysLTS)，是花生四烯酸代谢的5-脂氧合酶(5-LO)途径形成的脂质介质。它们最初被认为具有强大的支气管收缩作用，后来被确定也能促进炎症、微血管通透性和粘液分泌。这些对哮喘病理生理如此重要的作用在很大程度上是通过连接CysLT受体1(CysLT(1))来介导的。CysLT(1)的拮抗和5-LO的抑制都被证明在哮喘的治疗中有临床应用，但在对这些药物的反应中观察到显著的个体间异质性。本文就LTS的生物学作用、其生物合成途径和同源受体、现有抗LT药的药理作用以及抗LT药作为单一疗法和联合疗法治疗哮喘的临床证据作一综述。我们还考虑了反应的异质性，CysLT受体的可能作用，而不是CysLT(1)，另一类LT，LTB4的作用，以及LTS在哮喘以外的肺部疾病中的潜在作用。
Leukotrienes (LTs) C4, D4, and E4, collectively termed cysteinyl LTs (cysLTs), are lipid mediators formed by the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism. Originally recognized for their potent bronchoconstrictor actions, they were subsequently determined also to promote inflammation, microvascular permeability, and mucus secretion. These actions that are so central to asthma pathophysiology are mediated to a significant extent by ligation of the cysLT receptor 1 (CysLT(1)). Antagonism of CysLT(1) and inhibition of 5-LO have both been shown to have clinical use in the management of asthma, but substantial interindividual heterogeneity is observed in the response to these agents. In this article, we review the biologic actions of LTs, their biosynthetic pathways and cognate receptors, the pharmacology of available anti-LT agents, and the clinical evidence for the use of anti-LT agents as monotherapy and combination therapy in asthma. We also consider heterogeneity of response, the possible roles of cysLT receptors other than CysLT(1), the role of another class of LT, LTB4, and the potential role of LTs in lung diseases other than asthma.