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

Clin Exp Allergy. 2003 Mar;33(3):359-66. doi: 10.1046/j.1365-2222.2003.01615.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / administration & dosage*
  • Acetates / pharmacokinetics
  • Administration, Inhalation
  • Animals
  • Asthma / drug therapy*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Chemokines, CC / genetics*
  • Cyclopropanes
  • Eosinophils*
  • Humans
  • Immunoglobulin E / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism
  • Leukocyte Count
  • Leukotriene Antagonists / administration & dosage*
  • Leukotriene Antagonists / pharmacokinetics
  • Mice
  • Mice, Inbred BALB C
  • Models, Animal
  • Ovalbumin / immunology
  • Quinolines / administration & dosage*
  • Quinolines / pharmacokinetics
  • Quinolines / pharmacology*
  • RNA, Messenger / metabolism
  • Sulfides
  • Th2 Cells / immunology
  • Vascular Cell Adhesion Molecule-1 / immunology
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Acetates
  • Chemokines, CC
  • Cyclopropanes
  • Interleukins
  • Leukotriene Antagonists
  • Quinolines
  • RNA, Messenger
  • Sulfides
  • Vascular Cell Adhesion Molecule-1
  • Immunoglobulin E
  • Ovalbumin
  • montelukast