Published ahead of print on September 17, 2002, doi:10.1164/rccm.200205-387OC Am. J. Respir. Crit. Care Med., Volume 166, Number 11, December 2002, 1457-1460 A more recent version of this article appeared on December 1, 2002
Submitted on May 3, 2002 Montelukast Prevents Antigen-induced Mucociliary Dysfunction in SheepJuan R Sabater1,1 Research, Mount Sinai Medical Center, Miami Beach, Florida, USA, 2 Pulmonary and Critical Care Medicine, University of Miami School of Medicine, Miami, Florida, USA * To whom correspondence should be addressed. 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 if 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 8h after antigen challenge in six animals treated with montelukast (0.15 mg/kg, iv) 30 min before, 1h after, or 4h after antigen challenge. In the control trial, the sheep received 0.9% saline, iv, at each of the above time points. The maximum decrease in tracheal mucus velocity seen in the control trial was 56±4% (mean ±SE) of baseline at 8h. Pretreatment with montelukast significantly protected against this reduction. However, treatment at 1 and 4h 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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