In a new model using conscious, unrestrained and
ovalbumin-sensitized guinea pigs, we investigated the effects of the selective
histamine H1 receptor antagonist,
mepyramine, on the development of
allergen-induced early and late asthmatic reactions,
bronchial hyperreactivity and airway
inflammation, having each animal as its own control. In guinea pigs responding to a first
allergen exposure with an early as well as a late asthmatic reaction (82% of the animals) a second, identical,
allergen provocation was performed, in the absence (control) or presence of 1 mg/ml
mepyramine aerosol, inhaled for 10 min, 1 h before provocation. The
mepyramine treatment significantly reduced both early and late asthmatic reactions and prevented the development of
bronchial hyperreactivity to
histamine and
methacholine after both reactions. Examination of the bronchoalveolar lavage fluid 24 h after the second
allergen provocation revealed a general reduction of inflammatory cells after
mepyramine treatment. The results indicate that
histamine, released during the early asthmatic reaction, contributes to the development of the late asthmatic reaction as well as of early and late
bronchial hyperreactivity, possibly via an effect on airway
inflammation.