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American journal of respiratory and critical care medicine

Antileukotriene agents for the treatment of lung disease.


PMID 23822826

Abstract

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 (CysLT1). Antagonism of CysLT1 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 CysLT1, the role of another class of LT, LTB4, and the potential role of LTs in lung diseases other than asthma.