ROLE OF HISTAMINE IN ALLERGEN-INDUCED ASTHMATIC REACTIONS, BRONCHIAL HYPERREACTIVITY AND INFLAMMATION IN UNRESTRAINED GUINEA-PIGS

In a new model using conscious, unrestrained and ovalbumin-sensitized guinea pigs, we investigated the effects of the selective histamine H, receptor antagonist, mepyramine, on the development of allergen-induc ed early and late asthmatic reactions, bronchial hyperreactivity and a irway inflammation, having each animal as its own control. In guinea p igs responding to a first allergen exposure with an early as well as a late asthmatic reaction (82% of the animals) a second, identical, all ergen provocation was performed, in the absence (control) or presence of 1 mg/ml mepyramine aerosol, inhaled for 10 min, 1 h before provocat ion. The mepyramine treatment significantly reduced both early and lat e asthmatic reactions and prevented the development of bronchial hyper reactivity to histamine and methacholine after both reactions. Examina tion of the bronchoalveolar lavage fluid 24 h after the second allerge n provocation revealed a general reduction of inflammatory cells after mepyramine treatment. The results indicate that histamine, release du ring the early asthmatic reaction, contributes to the development of t he late asthmatic reaction as well as of early and late bronchial hype rreactivity, possibly via an effect on airway inflammation.