Montelukast prevents antigen-induced mucociliary dysfunction in sheep

Juan R Sabater, Adam Wanner, William W Abraham

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1457-1460
Number of pages4
JournalAmerican journal of respiratory and critical care medicine
Volume166
Issue number11
DOIs
StatePublished - Dec 1 2002

Keywords

  • Animal model
  • Asthma
  • Leukotrienes
  • Mucus
  • Therapy

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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