Interleukin-8 inhalation directly provokes bronchoconstriction in guinea pigs.

Abstract

Although it has been reported that the concentration of interleukin (IL)-8 in nasal lavage fluid and sputum and its production in bronchial epithelium were increased in asthmatic subjects, the direct effects of IL-8 on the airways in vivo is unclear. We examined bronchoconstriction in response to IL-8 inhalation through an endotracheal cannula in anesthetized, artificially ventilated guinea pigs. Inhalation of IL-8 at concentrations of 1 and 10 microg/ml caused significant bronchoconstriction, as revealed by the elevation of pressure at the airway opening. Moreover, the bronchoconstriction induced by IL-8 was significantly inhibited by the antihistamines diphenhydramine and terfenadine, suggesting the involvement of histamine release in the IL-8-induced bronchoconstriction. No significant leukocyte infiltration was observed in the bronchoalveolar lavage fluid or histologic findings 25 min after the first IL-8 inhalation. IL-8 provokes bronchoconstriction without leukocyte accumulation in the airways, mediated in part by histamine release, in guinea pigs.