Shuji Yamaguchi, Masahiko Kagoshima, Shin Kohge and Michio Terasawa
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., 955
Koiwai, Yoshitomi-cho, Chikujo-gun, Fukuoka 871, Japan
Abstract: We studied the effects of (+/-)-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
(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.
Keywords: Y-24180, Platelet-activating factor (PAF)-receptor antagonist,
Eosinophil, Interleukin-5