Effect of TYB-2285 on antigen-induced accumulation of eosinophils into the peritoneal cavity of rats sensitized with Ascaris suum extract.
1. The present study was carried out to investigate the effect of 3,5-bis-(acetoxyacetylamino)-4-chloro-benzonitrile (TYB-2285) on the accumulation of eosinophils in the peritoneal cavity of Wistar rats sensitized with Ascaris suum extract (Asc). 2. Rats were sensitized by IP injection of Asc on day 0 and were challenged by IP injection of Asc on day 7. Antigen challenge caused a specific, delayed infiltration of eosinophils into the peritoneal cavity that was inhibited by PO administration of TYB-2285, but not ketotifen fumarate, in a dose-dependent manner (3-30 mg/kg). 3. TYB-2285 inhibited the infiltration of eosinophils when during the induction phase, but not during the effector phase. The inhibitory effect of TYB-2285 when during the induction phase was stronger than any other antiallergic drugs, such as tranilast, azelastine, ibudilast, repirinast, tazanolast, oxatomide, or pemirolast. 4. Transfer of lymphocytes, but not serum, from sensitized rats to intact rats provoked a remarkable infiltration of eosinophils after the antigen challenge. In the experiment of adoptive transfer in rats, TYB-2285 was effective when given to donor rats. 5. These results demonstrate that TYB-2285 inhibits the accumulation of eosinophils presumably by inhibiting antigen recognition.
Tominaga
T
T
Department of Pharmacology, Pharmaceuticals Research Center, Toyobo Co. Ltd., Shiga, Japan.
Watanbe
A
A
Tsuji
J
J
Koda
A
A
Nagai
H
H
Kumazawa
Y
Y
Shimada
H
H
D019264:Adoptive Transfer; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000947:Antigens, Helminth / Q000276:immunology; D017165:Ascaris suum / Q000276:immunology; D004802:Eosinophilia / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D010529:Peritoneal Cavity / Q000166:cytology; D010533:Peritoneal Lavage; D051381:Rats; D017208:Rats, Wistar
D018926:Anti-Allergic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000947:Antigens, Helminth; D009570:Nitriles; C081050:3,5-bis(acetoxyacetylamino)-4-chlorobenzonitrile