Role of leukotrienes in asthma

Abstract

The allergen-induced release of leukotrienes, the 5-lipoxygenase products of arachidonic acid metabolism in activated airway cells, is critical in the pathophysiology of asthma. Key proteins in leukotriene formation are 5-lipoxygenase and 5-lipoxygenase-activating protein. The leukotrienes have potent biologic activity: leukotriene (LT)B4 is a chemoattractant for leukocytes and also induces leukocyte aggregation and adherence to vascular endothelium; and the sulfidopeptide leukotrienes, LTC4, LTD4, and LTE4 are bronchoconstrictors, induce airway mucous secretion, and increase vascular permeability. Sulfidopeptide leukotriene release has also been shown to be important in the pathogenesis of asthmatic aspirin intolerance. Effective, selective inhibitors of 5-lipoxygenase and 5-lipoxygenase-activating protein and leukotriene receptor antagonists have recently been developed as novel therapies for bronchial asthma and other inflammatory disorders.