Late phase bronchoconstriction and eosinophilia as well as methacholine hyperresponsiveness in Ascaris-sensitive rhesus monkeys were reversed by oral administration of U-83836E

• Published in: International archives of allergy and immunology Vol. 100; no. 4; p. 362
• Main Authors: Johnson, H G, Stout, B K
• Format: Journal Article
• Language: English
• Published: Switzerland 01.01.1993
• Subjects: Animals; Ascaris - immunology; Asthma - drug therapy; Asthma - physiopathology; Bronchial Provocation Tests; Bronchoconstriction - drug effects; Chromans - pharmacology; Eosinophilia - drug therapy; Female; Macaca mulatta; Methacholine Chloride - pharmacology; Piperazines - pharmacology
• ISSN: 1018-2438
• DOI: 10.1159/000236439

We used the Ascaris-sensitive primate model to assess the effect of oral doses of the 2-aminochroman (U-83836E) lazaroid on the antigen-induced late phase (24 h) bronchoconstriction (LPBC), eosinophilia and methacholine hyperreactivity. Following establishment of consistent lung resistance measurements and bronchoalveolar lavage eosinophilia in 4 Ascaris reactor primates, we determined the baseline aerosol mecholyl provocative challenge for 50% increase (PC50 in mg/ml) in these animals. Twenty-four hours following antigen challenge, we again determined the PC50 (mg/ml). In all 4 animals, there was a statistically significant decrease in PC50 (5.4- to 32-fold, n = 5-7; p < 0.029). Bronchoconstriction at 24 h increased in all 4 (49-86% over saline aerosol, p < 0.05). Eosinophilia increased from 21 to an average of 33% of total cells (p < 0.05 compared to saline). Repeating the antigen challenge in the presence of oral doses of 10 mg/kg U-83836E 18 and 3 h before and 6 h after challenge resulted in 53-70% inhibition of LPBC, 53-81% inhibition of eosinophilia (p < 0.05 compared to Ascaris) and return of the mecholyl PC50 (mg/ml) to before antigen levels (p = NS) thus blocking increased hyperreactivity. These results indicate U-83836E, like steroids, would be an effective drug for asthma and lung inflammation.