Expanding roles for leukotrienes in airway inflammation

Abstract

Leukotrienes (LTs) are lipid mediators derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. Cysteinyl (cys) LTs C(4), D(4), and E(4) are long known to contribute to airway contractile responses via ligation of the cysLT1 receptor, and cysLT1 antagonists are beneficial in some patients with asthma. Research advances over the past several years suggest that cysLT1 also mediates the ability of cysLTs to modulate inflammation, immune responses, and airway remodeling. Although less is known about an additional receptor, cysLT2, emerging evidence indicates that it likely also contributes to cysLT actions promoting inflammation, vascular permeability, and perhaps fibrosis. LTB(4), best known as a neutrophil chemoattractant, is now recognized to exert other important effects contributing to inflammatory and immune responses. These recent data highlight a growing appreciation for LTs as pleiotropic effectors, which are integral components in the network of molecules that mediate the expression of asthma.