Leukotrienes and airway inflammation

BackgroundAsthma is a common chronic inflammatory disease of the airways characterized by airway obstruction and hyperresponsiveness. Leukotrienes (LTs) are lipid mediators that contribute to many aspects of asthma pathogenesis. As the LT pathway is relatively steroid-resistant, its blockade by alternative strategies is a desirable component of asthma management. Cysteinyl LT (cysLT) receptor 1 antagonists (LTRAs) have been utilized worldwide for more than 10 years, and while their efficacy in asthma is well accepted, their limitations are also evident.Scope of ReviewIn this review, we summarize the biological effects of LTs in asthma, review recent advances in LT receptors, and consider possible new therapeutic targets in the LT pathway that offer the potential to achieve better control of asthma in the future.Major ConclusionsCysLTs play pathogenetic roles in many aspects of asthma, and blockade of cysLT receptor 1 by currently available LTRAs is certainly beneficial in disease management. On the other hand, the limitations of LTRAs are also apparent. Recent studies have revealed new receptors for cysLTs other than classical cysLT receptors 1 and 2, as well as the potential importance of LTB4 in asthma.General SignificanceRecent findings provide clues to new approaches for targeting the LT pathway that may overcome the current limitations of LTRAs and achieve superior control of asthma. This article is part of a Special Issue entitled: Biochemistry of Asthma.

Research Highlights
► CysLTs play pathogenetic roles in many aspects of asthma.
► While efficacious, limitations of LTRAs are also evident.
► Recent studies have revealed new receptors for cysLTs.
► The potential importance of LTB4 in asthma is also recognized.
► Recent findings provide a basis for new strategies for targeting of the LT pathway.