Comparison of the airway hyperreactivity produced by single and multiple antigen exposures in sensitized guinea pigs.
Chronic airway hyperreactivity is a hallmark feature of asthma, but animal models of airway hyperreactivity often utilize a single antigen challenge. Therefore, we compared the airway hyperreactivity produced by single and multiple antigen challenges in ovalbumin-sensitized guinea pigs. Significant (2-fold) leftward shifts in dose-response curves for i.v. methacholine- or LTD4-induced bronchoconstriction in anesthetized and ventilated animals occurred 24 h following a single ovalbumin challenge. This nonspecific airway hyperreactivity was prevented by pretreatment with ketotifen or dexamethasone. However, airway hyperreactivity was no greater 24 h following the last of 3 daily antigen challenges than after 1 challenge and was absent 72 h following one antigen challenge. These results raise concern over the similarity of antigen-induced airway hyperreactivity in guinea pigs to the chronic airway hyperreactivity in asthmatics.
Howell
R E
RE
Wyeth-Ayerst Research, Princeton, NJ 08543.
Sickels
B D
BD
Weichman
B M
BM
D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology*; D003907:Dexamethasone / Q000494:pharmacology; D006168:Guinea Pigs; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D011738:Pyrilamine / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology
D000941:Antigens; D008688:Methacholine Compounds; D013189:SRS-A; D003907:Dexamethasone; D010047:Ovalbumin; D011738:Pyrilamine; D007665:Ketotifen