Inhibition of airway hyperreactivity, edema, and lung cell infiltration bycompound U-83836E in sensitized guinea pigs

Sensitized guinea pigs were used to assess the effect of treatment with the compound U-83836E ((-)-2-[[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piper azinyl]methyl]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol, dihydr ochloride) on the antigen-induced late-phase (16 h) airway hyperreactivity, increase in inflammatory cell number, edema, and release of inflammatory m ediators in the bronchoalveolar lavage (BAL) fluid. After antigen challenge , an increase of the in vitro reactivity of the trachea and upper bronchi t o acetylcholine and histamine and an increase in the number of leukocytes i n the BAL fluid, mainly eosinophils and mononuclear cells, were observed. T he concentrations of proteins, histamine, and PGE, in the BAL fluid were al so significantly increased by 53, 57, and 216%, respectively, after antigen challenge. Treatment with U-83836E (10 mg/kg) given i.p. 17 and 3 h before and 6 h after antigen challenge inhibited by approximately 80% the total c ell number in the airways and the BAL fluid protein content. Moreover, this treatment totally inhibited airway hyperreactivity. Histamine and PGE(2) l evels in the BAL fluid were not significantly affected by U-83836E treatmen t. These results indicate that U-83836E is effective against some of the ch aracteristic features of asthma in ovalbumin-sensitized guinea pigs.