Leukotrienes as mediators of asthma

This review describes the aspects of leukotriene (LT) pharmacology and biology that are relevant to their important role in asthma. The biosynthesis and metabolism, including transcellular metabolism, of LTB4 and the cysteinyl-LTs (i.e. LTC4, LTD4 and LTE4) are described, and their transport is briefly outlined. The existence, distribution and pharmacological characterization of the receptors (BLT, CysLT1, CysLT2), as well as the transduction mechanisms triggered, are discussed in detail. We also describe their effects on airway smooth muscle tone, hyperresponsiveness and proliferation, on vascular tone and permeability, on mucus secretion, on neural fibers and inflammatory cell functions. Finally, the evidence supporting their role as asthma mediators is reviewed, including the effects of anti LT drugs (both biosynthesis inhibitors and receptor antagonists) in experimental and clinical asthma.