Suppressive effects of Y-24180, a long-acting antagonist for platelet-activating factor, on allergic pulmonary eosinophilia in mice.
We studied the effects of (+/-)-4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethy l-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (Y-24180), a long-acting antagonist for platelet-activating factor (PAF), on antigen-induced eosinophil infiltration and interleukin-5 (IL-5) release in the bronchoalveolar lavage fluid (BALF) of mice. Mice actively sensitized with ovalbumin (OA) were challenged by injecting intratracheally OA 3 times every fourth day. Both the number of eosinophils and level of IL-5 were significantly increased in the BALF 24 hr after the last OA challenge. Either Y-24180 or prednisolone was orally administered once a day for 10 days beginning one day before the first OA challenge. WEB2086, another PAF antagonist, was orally administered once or twice a day for 10 days. Y-24180 (0.3 - 3 mg/kg) suppressed the eosinophil infiltration in a dose-dependent manner and suppressed the IL-5 release at the highest dosage. Prednisolone (10 mg/kg) significantly suppressed both the eosinophil infiltration and IL-5 release. In contrast, WEB2086 affected neither the eosinophil infiltration nor IL-5 release when administered once a day (10 - 100 mg/kg/day). This drug never affected the IL-5 release but significantly suppressed eosinophil infiltration even when administered twice a day (30 - 200 mg/kg/day). These results indicate that the suppressive effect of Y-24180 on allergic pulmonary eosinophilia is due to not only to its long-lasting PAF-antagonism but also due to its suppressive effect on IL-5 release.
Yamaguchi
S
S
Research Laboratories, Yoshitomi Pharmaceutical Industries Ltd., Fukuoka, Japan.
Kagoshima
M
M
Kohge
S
S
Terasawa
M
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001249:Asthma / Q000378:metabolism / Q000517:prevention & control*; D001381:Azepines / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004804:Eosinophils / Q000166:cytology; D015848:Interleukin-5 / Q000737:chemistry / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011239:Prednisolone / Q000627:therapeutic use; D011657:Pulmonary Eosinophilia / Q000378:metabolism / Q000517:prevention & control*; D014230:Triazoles / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D001381:Azepines; D015848:Interleukin-5; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C052518:WEB 2086; C068035:4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine; D011239:Prednisolone