THE EFFECT OF THE SELECTIVE PAF ANTAGONIST WEB-2170 ON PAF AND ANTIGEN-INDUCED AIRWAY HYPERRESPONSIVENESS AND EOSINOPHIL INFILTRATION

Exposure of normal guinea pigs to an aerosol of PAF induced an increase in airway responsiveness to i.v. histamine, 24 h and 48 h post challenge compared to animals that received BSA alone. There was no significant alteration in airway responsiveness 1 h, 4 h or 72 h after PAF challenge. Exposure of actively sensitised guinea pigs to an aerosol of ovalbumin induced airway hyperresponsiveness to i.v. histamine, 24 h post challenge. PAF induced a selective increase in the percentage of eosinophils in bronchoalveolar lavage fluid 24 h after challenge, that persisted for at least 72 h post challenge. No significant increase in eosinophils was noted 1-4 h after PAF exposure. Antigen challenge of actively sensitised guinea pigs induced a significant increase in the percentage of eosinophils recovered in BAL fluid 24 h post challenge. Pretreatment of both normal and sensitised guinea pigs with the selective PAF antagonist WEB 2170 significantly inhibited both airway hyperresponsiveness and airway eosinophilia 24 h post challenge with aerosol PAF or allergen. These results further support the suggestion that PAF may play a central role in allergen induced eosinophil infiltration and airway hyperresponsiveness in the guinea pig.