Role of leukotrienes in asthma pathophysiology

inflammation is an essential component of asthma pathophysiology. While bet a(2)-agonists are often used for short-term relief of acute bronchospasm, a nti-inflammatory agents are required for the long-term management of chroni c inflammation in this disease. Corticosteroids have emerged as the first-l ine anti-inflammatory therapy for asthma management. However, in some patie nts, especially children, the high doses of corticosteroids that may be req uired to control features of hyperresponsiveness, including exercise-induce d asthma, raise safety concerns. Thus, there is a need for complementary an ti-inflammatory, steroid-sparing agents in asthma therapy. Several inflamma tory mediators have been targeted in an attempt to thwart this inflammatory process, but so far with little success. The cysteinyl leukotrienes (CysLT), LTC4, LTD4, and LTE4, have been shown t o be essential mediators in asthma, making them obvious targets for therapy . These cysteinyl leukotrienes, previously known as the slow-reacting subst ance of anaphylaxis (SRS-A), mediate many of the features of asthma, includ ing bronchial constriction, bronchial hyperreactivity, edema, and eosinophi lia. Data show that selective cysteinyl leukotriene receptor antagonists (C ysLTRAs) effectively reverse these pathologic changes. Corticosteroids do n ot inhibit the production of CysLTs in vivo, suggesting that CysLTRAs and c orticosteroids affect different targets. The bronchodilator properties of C ysLTRAs seem to be additive to those of beta(2)-agonists and corticosteroid s. These data suggest that CysLTs are important therapeutic targets in the man agement of inflammation in asthma. (C) 2000 Wiley-Liss, Inc.