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Anti‐inflammatory effects of high‐dose montelukast in an animal model of acute asthma
Author(s) -
Wu A. Y.,
Chik S. C.,
Chan A. W.,
Li Z.,
Tsang K. W.,
Li W.
Publication year - 2003
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.2003.01615.x
Subject(s) - eotaxin , bronchoalveolar lavage , medicine , ovalbumin , immunology , inflammation , chemokine , lung , immunoglobulin e , montelukast , eosinophil , asthma , immune system , antibody
Summary Background Asthmatic inflammation is mediated by a network of cytokines, chemokines and adhesion molecules. Corticosteroids are the only effective agents available to control asthmatic inflammation. We investigated the effect of high‐dose montelukast (MK), a selective cysteinyl leukotriene receptor 1 antagonist, on mediators of airway inflammation. Objective The aim of this study was to determine the effect of a 3‐day course of high‐dose MK on mediators of airway inflammation induced by a single allergen challenge in sensitized mice. Methods Ovalbumin (OVA)‐sensitized BALB/c mice were treated with 25 mg/kg of MK or saline intravenously for 3 days. On the third day, a single inhalation challenge with OVA was given. Cellular infiltration was assessed in the bronchoalveolar lavage (BAL) and in the lung. Expression of IL‐4, IL‐5, IL‐13 and eotaxin in the BAL, and the lung was determined. Serum IL‐5 and total IgE was measured. IL‐5 and eotaxin mRNA expression in the lung was determined. Finally, eotaxin and VACM‐1 expression in the lung was assessed by immunohistochemistry. Results MK reduced the number of eosinophils in the BAL by > 90%. There was also significant reduction in IL‐5 in the BAL, lung and the serum, and IL‐5 mRNA expression in the lung. IL‐4 level in the lung and BAL, and IL‐13 level in the lung also significantly decreased. Serum IgE level and lung VCAM‐1 expression was also significantly lower in treated animals, but eotaxin protein and mRNA expression in the lung remained unchanged. Conclusion MK exerts its anti‐inflammatory effect through the suppression of T helper type‐2 (Th2) cytokines. The use of high‐dose MK as an anti‐inflammatory agent in acute asthma should be further explored.