Leukotrienes and Antileukotriene Therapy in Allergic Rhinitis

Abstract

Leukotrienes (LT) are the inflammatory mediators that have an important role in inflammatory diseases such as allergic rhinitis and asthma. The leukotrienes that contain cystein, cysteinyl leukotrienes (Cys LTs), are LTC4, LTD4 and LTE4. They are synthesized from arachidonic acid by 5-lipooxygenase pathway and eosinophils and mast cells can produce large amounts of Cys LTs from an endogenous pool of arachidonic acid. Cys LTs exert their effects by binding to their receptors namely Cys LT1 and Cys LT2 receptors. They contribute the allergic inflammation by promoting inflammatory cell recruitment and activation, enhancing production of certain cytokines that play a role in allergic inflammation, promoting fibrosis and airway remodeling in bronchi, inducing vascular leakage and vasodilatation leading to mucosal edema especially in nasal mucosa, stimulating mucus secretion by goblet cells and decreasing mucociliary clearance. The main symptom of allergic rhinitis related to Cys LTs seems to be nasal congestion. In allergic rhinitis, monotherapy with a Cys LT1 receptor anatagonist is better than placebo and equivalent to oral antihistamine therapy. Combination of LT1 receptor antagonists and oral antihistamines are superior to antihistamines alone. Intranasal corticosteroids alone are more effective than both LT1 receptor antagonists alone and the combination of LT1 eceptor antagonists with antihistamines. Clarification of the actions of Cys LTs mediated by Cys LT2 receptor and other possible receptors and further development of antagonists against those receptors might increase the efficacy of antilekotriene therapy on the symptoms of allergic rhinitis.