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Montelukast prevents antigen-induced mucociliary dysfunction in sheep
Juan R Sabater1, Adam Wanner, William M Abraham
1Division of Pulmonary and Critical Care Medicine, University of Miami at Mount Sinai Medical Center, Miami Beach, Florida 33140, USA.
American Journal of Respiratory and Critical Care Medicine
|October 31, 2002
Summary
Montelukast pretreatment prevented antigen-induced impairment of tracheal mucus velocity in sheep. However, later administration of montelukast did not reverse this mucociliary dysfunction, suggesting early cysteinyl leukotriene release is key.
Area of Science:
- Respiratory Medicine
- Immunology
- Pharmacology
Background:
- Cysteinyl leukotrienes are potent inflammatory mediators implicated in asthma pathophysiology.
- Mucociliary dysfunction is a critical component of asthma, impacting airway clearance.
Purpose of the Study:
- To investigate the effect of montelukast, a cysteinyl leukotriene 1 receptor antagonist, on antigen-induced mucociliary dysfunction in allergic sheep.
- To determine if montelukast could prevent or reverse impaired tracheal mucus velocity following antigen challenge.
Main Methods:
- Allergic sheep were challenged with antigen, and tracheal mucus velocity (a marker of mucociliary clearance) was measured.
- Montelukast was administered intravenously at different time points: 30 minutes before, 1 hour after, or 4 hours after antigen challenge.
- Control animals received saline, and changes in tracheal mucus velocity were compared across groups.
Main Results:
- Antigen challenge significantly reduced tracheal mucus velocity by 56% in control sheep.
- Pretreatment with montelukast (30 minutes before antigen challenge) significantly protected against this reduction in tracheal mucus velocity.
- Administration of montelukast 1 or 4 hours after antigen challenge did not prevent or reverse the decrease in tracheal mucus velocity.
Conclusions:
- Early release of cysteinyl leukotrienes contributes to the acute fall in tracheal mucus velocity after antigen challenge.
- Pretreatment with montelukast effectively reduces antigen-induced impairment of mucociliary clearance in this asthma model.
- Therapeutic timing is critical for montelukast's efficacy in mitigating leukotriene-mediated airway dysfunction.