Interleukin-8 inhalation directly provokes bronchoconstriction in guinea pigs

Background: Although it has been reported that the concentration of interle ukin (IL)-8 in nasal lavage fluid and sputum and its production in bronchia l epithelium were increased in asthmatic subjects, the direct effects of IL -8 on the airways in vivo is unclear. Methods: We examined bronchoconstriction in response to IL-8 inhalation thr ough an endotracheal cannula in anesthetized, artifically ventilated guinea pigs. Results: Inhalation of IL-8 at concentrations of 1 and 10 mu g/ml caused si gnificant bronchoconstriction, as revealed by the elevation of pressure at the airway opening. Moreover, the bronchoconstriction induced by IL-8 was s ignificantly inhibited by the antihistamines diphenhydramine and terfenadin e, suggesting the involvement of histamine release in the IL-8-induced bron choconstriction. No significant leukocyte infiltration was observed in the bronchoalveolar lavage fluid or histologic findings 25 min after the first IL-8 inhalation. Conclusions: IL-8 provokes bronchoconstriction without leukocyte accumulati on in the airways, mediated in part by histamine release, in guinea pigs.