Leukotriene B₄ induces airway hyperesponsiveness 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.