EFFECTS OF TYB-2285 ON THE ACCUMULATION OF EOSINOPHILS IN THE AIRWAY INDUCED BY ANTIGEN EXPOSURE IN ACTIVELY SENSITIZED BROWN-NORWAY RATS

I, The effect of TYB-2285 on the antigen induced accumulation of eosin ophils into the airway was investigated in two models (inhalant sensit ization and noninhalant sensitization) using Brown Norway (BN) rats. 2 . In the method of inhalant sensitization, BN rats were sensitized by weekly exposure to ovalbumin (OA). The accumulation of eosinophils was inhibited by the oral administration of TYB-2285 for the first 2 days of each sensitization in a dose dependent manner. 3. With noninhalant sensitization, BN rats were sensitized by TM injection of OA and TP i njection of killed Bordetella pertussis. The accumulation of eosinophi ls was inhibited by TYB-2285 in a dose-dependent manner, when TYB-2285 is given PO 5 mm before and 5 hr after the antigen exposure. Moreover , this accumulation of eosinophils was inhibited by a single administr ation of TYB-2285 5 hr after the antigen exposure, presumably when the mast cell degranulation was already finished. 4. In the method with n oninhalant sensitization, the accumulation of eosinophils was not inhi bited by mast cell stabilizers such as ketotifen, tranilast, or DSCG. 5. The present study demonstrates that TYB-2285, unlike other mast cel l stabilizers, inhibits the antigen-induced accumulation of eosinophil s into the airway. It also suggests that this drug might be effective in asthmatic patients. Copyright (C) 1997 Elsevier Science Inc.