Leukotriene B4 induces airway hyperresponsiveness in dogs

We studied the effect of leukotriene B4 aerosols on airway responsiveness to inhaled acetylcholine aerosols and on the cellular components and cyclooxygenase metabolites in bronchoalveolar lavage fluid in dogs. Inhalation of leukotriene B4 aerosols had no effect on resting total pulmonary resistance but increased airway responsiveness, an effect that was maximum in 3 h and that returned to control levels within 1 wk. Three hours after leukotriene B4, the number of neutrophils and the concentration of thromboxane B2 recovered in lavage fluid increased markedly. Pretreatment with the thromboxane synthase inhibitor OKY-046 prevented the increases in airway responsiveness and in thromboxane B2 but did not alter neutrophil chemotaxis. Thus we speculate that leukotriene B4 causes neutrophil chemotaxis and release of thromboxane B2, which increases airway responsiveness.