Modification of Allergen-induced Airway Obstruction and Airway Hyperresponsiveness in an Allergic Rabbit Model by the Selective Platelet-activating Factor Antagonist, BN 52021

Allergen challenge of eight ragweed-immunized rabbits elicited a prolonged airway obstruction that was evident during the 6-hour study period. Airway responsiveness to histamine was enhanced 24 hours after allergen exposure (geometric mean of the 50% reduction in effective dose [ED50] of dynamic compliance [Cdyn] before challenge, 3.46 mg/ml, decreased to 0.52 mg/ml after challenge, p less than 0.01; pulmonary resistance ED50 geometric mean before challenge, 3.50 mg/ml, decreased to 0.65 mg/ml after challenge, p less than 0.05). In a random crossover study, the selective platelet-activating factor antagonist, BN 52021 (60 mg/kg, orally, 1 hour before allergen challenge), significantly reduced the allergen-induced airway obstruction (p less than 0.005). In addition, pretreatment with BN 52021 reduced the associated increased airway responsiveness induced by allergen exposure (prechallenge Cdyn ED50, 1.93; after challenge, 2.13 mg/ml; pulmonary resistance ED50, 1.91 mg/ml before challenge and 1.69 mg/ml after challenge). These present observations suggest a role for platelet-activating factor in the pathogenesis of allergen-induced airway obstruction and in the development of airway hyperresponsiveness in an allergic rabbit model.