NEUTROPHIL-INDUCED HUMAN BRONCHIAL HYPERRESPONSIVENESS INVITRO - PHARMACOLOGICAL MODULATION

Although it has been postulated that inflammatory cells cause the bron chial hyperresponsiveness which is diagnostic of asthma [1], until rec ently there has been little direct evidence of such a link. We have re cently shown that calcium ionophore-activated human neutrophils and eo sinophils can induce a state of human airway hyperresponsiveness in vi tro [2]. In this study we have shown that the anti-inflammatory agent nedocromil sodium, 10(-7) M, inhibited the hyperresponsiveness induced by products released from ionophore activated neutrophils but did not inhibit the release of leukotriene B4 from the same cells. Neutrophil -induced bronchial hyperresponsiveness was also inhibited by pre-treat ment of the bronchial tissues with a thromboxane A2 and prostaglandin receptor antagonist, GR32191, 10(-7) m. These findings indicate that c yclooxygenase products are involved in bronchial hyperresponsiveness i nduced by inflammatory cell products in vitro and that their release c an be inhibited by nedocromil sodium.