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Montelukast Prevents Antigen-induced Mucociliary Dysfunction in Sheep

Division of Pulmonary and Critical Care Medicine, University of Miami at Mount Sinai Medical Center, Miami Beach, Florida

Correspondence and requests for reprints should be addressed to William M. Abraham, Ph.D., Department of Research, Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, FL 33140. E-mail: abraham{at}msmc.com

The cysteinyl leukotrienes are potent proinflammatory mediators that, in addition to their bronchospastic actions, can also contribute to mucociliary dysfunction, a central component of the pathophysiology of asthma. In this study, we determined whether montelukast, a cysteinyl leukotriene 1 receptor antagonist, could prevent and/or reverse antigen-induced mucociliary dysfunction in allergic sheep. We measured tracheal mucus velocity, a marker of mucociliary clearance, before and for 8 hours after antigen challenge in six animals treated with montelukast (0.15 mg/kg, intravenously) 30 minutes before, 1 hour after, or 4 hours after antigen challenge. In the control trial, the sheep received 0.9% saline intravenously at each of the previously mentioned time points. The maximum decrease in tracheal mucus velocity seen in the control trial was 56 ± 4% (mean ± SE) of baseline at 8 hours. Pretreatment with montelukast significantly protected against this reduction. However, treatment at 1 and 4 hours neither protected against nor reversed the allergen-induced fall in tracheal mucus velocity. We conclude that the early release of cysteinyl leukotrienes may contribute to the fall in tracheal mucus velocity that follows acute antigen challenge and that pretreatment with montelukast reduces this impairment.

Key Words: asthma • mucus • leukotrienes • animal model • therapy

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