Effects of single and multiple inhalations of antigen on airway responsiveness in monkeys.
Airway hyperresponsiveness is an important and characteristic feature of asthma. In monkeys, we have reported that antigen (Ag) inhalation induces a prolonged airway eosinophilia, that chronic airway eosinophilia is associated with marked airway hyperresponsiveness, and that chronic Ag inhalations induce airway eosinophilia and hyperresponsiveness. In this study we have determined the effects of acute Ag inhalation(s) on airway responsiveness to obtain a protocol for the study of the mechanisms involved. Anesthetized and intubated adult male cynomolgus monkeys with a naturally occurring sensitivity to Ascaris suum extract were studied. Airway responsiveness (provocative concentration of nebulized and inhaled methacholine that induced a 100% increase in respiratory system resistance [Rrs] [PC100]; twofold decrease regarded as significant) and airway cell composition (bronchoalveolar lavage [BAL]) were determined 1 day before and 20 hours after a single inhalation of Ascaris extract, or 3 days before and 3 days after three alternate-day inhalations of Ascaris extract. The single inhalation of Ag (N = 7) caused an acute increase in Rrs (307% +/- 62%), an increase in BAL leukocytes, and a decrease in PC100 in three animals that was moderate (more than eightfold) in two animals. The mean +/- SE change in log PC100 was only -0.25 +/- 0.24. The multiple inhalations of Ag in the same animals caused acute increases in Rrs (178% +/- 48%, 380% +/- 83%, and 331% +/- 63%, respectively), an increase in BAL granulocytes, and a decrease in PC100 in six of seven animals (mean +/- SE change in log PC100 was -1.36 +/- 0.34) that was moderate in two and severe (more than 80-fold) in three animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Wegner
C D
CD
Department of Pharmacology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.
Torcellini
C A
CA
Clarke
C C
CC
Letts
L G
LG
Gundel
R H
RH
D000280:Administration, Inhalation; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001980:Bronchi / Q000502:physiology*; D001985:Bronchial Provocation Tests; D008252:Macaca fascicularis; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage
D000941:Antigens; D016210:Methacholine Chloride