PHARMACOLOGICAL MODULATION OF ANTIGEN-INDUCED AIRWAY HYPERRESPONSIVENESS BY THROMBOXANE-A(2) INHIBITORS IN GUINEA-PIGS

The effects of OKY-046 (thromboxane A2 (TXA2) synthetase inhibitor) an d ONO-3708 (TXA2 receptor antagonist) on antigen-induced airway hyperr eactivity in guinea pigs were investigated. Ketotifen was used as a re ference drug. Seven inhalations of an antigen into actively sensitized animals resulted in an increase in airway reactivity to acetylcholine . Twenty-four hours after the final inhalation, the number of leukocyt es (macrophages, neutrophils, eosinophils and lymphocytes) and the qua ntity of mediators (thromboxane B2, leukotriene D4 and histamine) in b ronchoalveolar lavage fluid increased. All examined drugs inhibited th e antigen-induced airway hyperreactivity to acetylcholine. Whereas ket otifen inhibited an accumulation of inflammatory cells (eosinophils an d neutrophils) in bronchoalveolar lavage fluid, OKY-046 and ONO-3708 h ad no effect on the accumulation of inflammatory cells. OKY-046, but n ot ketotifen and ONO-3708, inhibited an increase of thromboxane B2 in the bronchoalveolar lavage fluid after antigen provocation. These resu lts suggest the participation of TXA2 in the onset of antigen-induced airway hyperresponsiveness in guinea pigs, and the efficacy of TXA2 in hibitors, without affecting the accumulation of inflammatory celts in bronchoalveolar lavage fluid.