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


CONCLUSIONS
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.
Wu
A Y
AY
Department of Medicine, University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, China. adrianwu@hku.hk
Chik
S C
SC
Chan
A W
AW
Li
Z
Z
Tsang
K W
KW
Li
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W
D000085:Acetates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D019742:Chemokines, CC / Q000235:genetics*; D003521:Cyclopropanes; D004804:Eosinophils; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count; D020024:Leukotriene Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin / Q000276:immunology; D011804:Quinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013440:Sulfides; D018418:Th2 Cells / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism
D000085:Acetates; D019742:Chemokines, CC; D003521:Cyclopropanes; D007378:Interleukins; D020024:Leukotriene Antagonists; D011804:Quinolines; D012333:RNA, Messenger; D013440:Sulfides; D019010:Vascular Cell Adhesion Molecule-1; D007073:Immunoglobulin E; D010047:Ovalbumin; C093875:montelukast