EFFECT OF THROMBOXANE A(2) ANTAGONISTS ON BRONCHIAL HYPERRESPONSIVENESS INDUCED IMMEDIATELY AFTER INTERLEUKIN-8 INHALATION IN GUINEA-PIGS

1 Although repeated intranasal administration of interleukin-8 (IL-8) causes bronchial hyperresponsiveness (BHR) mediated via thromboxane A( 2) (TXA(2)) and airway neutrophil accumulation in guineapigs, the acut e effect of inhaled IL-8 is unclear. We performed this study to clarif y the acute effect of IL-8 on bronchial responsiveness and the role of TXA(2). 2 The effects of inhaled IL-8 on bronchial responsiveness and of the TXA(2) antagonists, S-1452 (0.01 and 0.1 mg kg(-1)) and ONO-NT -126 (1.0 or 10 mu g kg(-1)), on IL-8-induced BHR were examined by use of a modified Konzett-Rossler method in guinea-pigs. 3 Inhaled IL-8 a t 100 ng ml(-1), which failed to induce significant changes in Pao (pr essure at the airway opening), enhanced an increase in Pao induced by subsequent inhalations of ascending doses (50-200 mu g ml(-1)) of meth acholine and histamine, suggesting the potentiating effect of IL-8 on bronchial responsiveness. No significant leukocyte infiltration was ob served histologically sixteen minutes after the IL-8 inhalation. Both S-1452 and ONO-NT-126 reduced the IL-8-induced BHR. 4 In conclusion, I L-8 rapidly causes BHR via TXA(2) release in guinea-pigs.