Role of cyclooxygenase and 5-lipoxygenase metabolites, platelet-activating factor and 5-hydroxytryptamine in allergen-induced airway responses in the brown Norway rat.

Abstract

We determined the effects of selective inhibition of arachidonic acid metabolism via the cyclooxygenase and 5'-lipoxygenase pathways using flurbiprofen and BWA4C, respectively, of 5-hydroxytryptamine (5-HT) using methysergide and of platelet-activating factor (PAF) using WEB 2086 on the airway responses to ovalbumin (OA) aerosol in OA-sensitized Brown Norway rats. Twenty-one days after intraperitoneal injection of OA, rats were exposed to a 1% OA or saline aerosol. Only methysergide (10 mg/kg i.p.; 3 doses over 24 h) provided significant protection of the immediate response to OA. The increase in airway responsiveness to acetylcholine after OA exposure was not significantly altered by methysergide, flurbiprofen (10 mg/kg i.p.), BWA4C (50 mg/kg i.p.) and WEB 2086 (50 mg/kg i.p.) all given over 24 h prior to OA challenge. In addition, there was no effect on the increased recovery of eosinophils and lymphocytes in bronchoalveolar lavage fluid at 24 h. We conclude that 5-HT is an important mediator of the acute response to OA, but that 5-HT, lipoxygenase and cyclooxygenase products and PAF are unlikely to be involved in OA-induced airway hyperresponsiveness and inflammation in the Brown Norway rat.