Effects of TYB-2285 on the accumulation of eosinophils in the airway induced by antigen exposure in actively sensitized brown Norway rats.
1. The effect of TYB-2285 on the antigen-induced accumulation of eosinophils into the airway was investigated in two models (inhalant sensitization 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 i.m. injection of OA and i.p. injection of killed Bordetella pertussis. The accumulation of eosinophils was inhibited by TYB-2285 in a dose-dependent manner, when TYB-2285 is given p.o. 5 mm before and 5 hr after the antigen exposure. Moreover, this accumulation of eosinophils was inhibited by a single administration of TYB-2285 5 hr after the antigen exposure, presumably when the mast cell degranulation was already finished. 4. In the method with noninhalant sensitization, the accumulation of eosinophils was not inhibited by mast cell stabilizers such as ketotifen, tranilast, or DSCG. 5. The present study demonstrates that TYB-2285, unlike other mast cell stabilizers, inhibits the antigen-induced accumulation of eosinophils into the airway. It also suggests that this drug might be effective in asthmatic patients.
Tominaga
T
T
Department of Pharmacology, Toyobo Co. Ltd., Shiga, Japan.
Watanabe
A
A
Tsuji
J
J
Koda
A
A
Nagai
H
H
Kumazawa
Y
Y
Shimada
H
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000941:Antigens / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D005260:Female; D008297:Male; D008407:Mast Cells / Q000276:immunology; D009570:Nitriles / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; D009570:Nitriles; C081050:3,5-bis(acetoxyacetylamino)-4-chlorobenzonitrile; D010047:Ovalbumin