Nasal secretion in ragweed-sensitized dogs: Effect of leukotriene synthesis inhibition

Allergic rhinitis is an inflammatory disease associated with local leukotri ene release during periods of symptoms. Zileuton, a leukotriene synthesis i nhibitor, is known to inhibit the release of leukotriene B-4. Because we pr eviously showed that leukotriene B-4 is a potent mediator of neutrophil-dep endent nasal secretion, we investigated whether Zileuton inhibited allergen -induced nasal secretion. Using a newly developed method for isolating and superfusing a nasal segment, we examined the effect of Zileuton on nasal se cretion and neutrophil recruitment in ragweed-sensitized dogs. Instillation of ragweed into the nasal segment caused lime-dependent increases in the v olume of airway fluid and the recruitment of neutrophils. Zileuton prevente d ragweed-induced neutrophil recruitment and nasal secretion. These results indicate that leukotrienes are important mediators of allergy-induced nasa l secretion in dogs. Future clinical studies in allergic patients will dete rmine whether there is a therapeutic role for leukotriene synthesis inhibit ors in modulating neutrophil recruitment and hypersecretion in the nose.