Leukotriene generation

Leukotriene modifier drugs do not cause bronchodilation in normal subjects, so the efficacy of therapy with leukotriene synthesis inhibitors (LTSI) and leukotriene receptor antagonists (LTRA) in asthmatic patients is a function of excessive leukotriene production and the responsiveness of asthmatic airways to these mediators. Clinical trials of LT modifier drugs in challenge models of asthma show that cys-LT synthesis represents a final common pathway for acute bronchoconstriction in response to allergic and nonallergic stimuli [1]. Increasingly, evidence suggests that in addition to these acute mast cell-dependent responses, chronic cys-LT production in asthma depends on infiltrating inflammatory cells including eosinophils, and even that cys-LT production by structural airway cells including bronchial epithelium, airway smooth muscle and vascular endothelium may contribute to airway remodelling. This review will focus on clinical, genetic and immunopathological studies that throw light on the mechanisms and cellular sources of excess cys-LT synthesis in the asthmatic lung