Titre du document / Document title

Anti-inflammatory effects of high-dose montelukast in an animal model of acute asthma

Auteur(s) / Author(s)

WU A. Y. ⁽¹⁾ ; CHIK S. C. ⁽¹⁾ ; CHAN A. W. ⁽¹⁾ ; LI Z. ⁽¹⁾ ; TSANG K. W. ⁽¹⁾ ; LI W. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Medicine, University of Hong Kong, HONG-KONG

Résumé / Abstract

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.

Revue / Journal Title

Clinical and experimental allergy   ISSN 0954-7894 

Source / Source

2003, vol. 33, n^o3, pp. 359-366 [8 page(s) (article)] (46 ref.)

Langue / Language

Anglais

Editeur / Publisher

Blackwell, Oxford, ROYAUME-UNI  (1989) (Revue)

Mots-clés anglais / English Keywords

Cytokine ; Chemokine ; Immunopathology ; Obstructive pulmonary disease ; Respiratory disease ; Vertebrata ; Mammalia ; Rodentia ; Cell adhesion molecule ; Vascular cell adhesion molecule 1 ; Interleukin 5 ; Leukotriene ; Biological receptor ; Interleukin 4 ; Antagonist ; Eotaxin ; Montelukast ; Mechanism of action ; High dose ; Chemotherapy ; Treatment ; Mouse ; Animal ; Animal model ; Allergy ; Asthma ;

Mots-clés français / French Keywords

Cytokine ; Chimiokine ; Immunopathologie ; Bronchopneumopathie obstructive ; Appareil respiratoire pathologie ; Vertebrata ; Mammalia ; Rodentia ; Protéine CAM ; Protéine VCAM1 ; Interleukine 5 ; Leucotriène ; Récepteur biologique ; Interleukine 4 ; Antagoniste ; Eotaxine ; Montélukast ; Mécanisme action ; Dose forte ; Chimiothérapie ; Traitement ; Souris ; Animal ; Modèle animal ; Allergie ; Asthme ;

Mots-clés espagnols / Spanish Keywords

Citoquina ; Quimioquina ; Inmunopatología ; Broncopneumopatía obstructiva ; Aparato respiratorio patología ; Vertebrata ; Mammalia ; Rodentia ; Proteína CAM ; Proteína VCAM1 ; Interleuquina 5 ; Leucotrieno ; Receptor biológico ; Interleuquina 4 ; Antagonista ; Eotaxina ; Montelukast ; Mecanismo acción ; Dosis fuerte ; Quimioterapia ; Tratamiento ; Ratón ; Animal ; Modelo animal ; Alergia ; Asma ;

Localisation / Location

INIST-CNRS, Cote INIST : 15394, 35400011073872.0160