Abstract
The effects of CS-518 (sodium 2-(1-imidazolylmethyl)-4,5-dihydrobenzo[b]thiophene-6-carboxylate), a thromboxane A 2 synthase inhibitor, on eosinophil accumulation and activation were investigated in an experimental asthmatic guinea pig model and several cellular models. In the in vivo studies, CS-518 inhibited the biphasic eosinophil accumulation in the bronchoalveolar lavage fluid, potently in the early phase, but less potently in the delayed phase. On the other hand, even at the lower dose, CS-518 completely inhibited the hypodensity of eosinophils in the delayed phase. In the in vitro studies, CS-518 suppressed thromboxane A 2 production and potentiated prostaglandin I 2 production from guinea pig eosinophils. Moreover, CS-518 and prostaglandin I 2 suppressed chemotaxis, peroxidase release and superoxide generation in guinea pig eosinophils. In addition, the present studies provide further support for the possibility that thromboxane A 2 and prostaglandin I 2, which are produced in bronchoalveolar tissue and within eosinophils, are involved in modulation of eosinophil function and suggest that CS-518 is a potent inhibitor of eosinophil activation.
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