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 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.
Santing
R E
RE
Department of Medicinal Chemistry and Molecular Pharmacology, University Centre for Pharmacy, Groningen, Netherlands.
Schraa
E O
EO
Wachters
A
A
Olymulder
C G
CG
Zaagsma
J
J
Meurs
H
H
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001991:Bronchitis / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid; D006168:Guinea Pigs; D006632:Histamine / Q000502:physiology*; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D011738:Pyrilamine / Q000494:pharmacology; D012129:Respiratory Function Tests
D000485:Allergens; D008688:Methacholine Compounds; D006632:Histamine; D010047:Ovalbumin; D011738:Pyrilamine