文章基本信息

标题：The Effect of a Newly Synthesized Indazole Compound, TAS-3-124, on Experimental Autoimmune Disease
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作者：Hirotomo Akabane ; Naoki Miyagawa ; Hiroaki Nii 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2004
卷号：27
期号：8
页码：1218-1223
DOI：10.1248/bpb.27.1218
出版社：The Pharmaceutical Society of Japan
摘要：The effects of a newly synthesized compound, 6-acetoamido-1-acetyl-1-indazole (TAS-3-124), on autoimmune diseases were studied. We used animal models of collagen-induced arthritis (CIA) in mice and experimental autoimmune encephalomyelitis (EAE) in rats to evaluate the efficacy of TAS-3-124. TAS-3-124 at doses of 100 and 300 mg/kg p.o. inhibited the development of CIA, decreasing the swelling of fore- and hind-limbs and bone destruction in knee joints. This agent also suppressed the delayed type hypersensitivity reaction (DTH) against type II collagen. These effects were confirmed by histopathological examination and measurement of the expression of mRNA of proinflammatory cytokines in the knee joint. In addition, TAS-3-124 at a dose of 300 mg/kg inhibited the development of EAE and the DTH to myelin basic protein (MBP) in rats. Moreover, TAS-3-124 inhibited the production of proinflammatory cytokines including interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 but not T cell derived cytokines in mice. These demonstrate the efficacy of TAS-3-124 against experimental autoimmune disease, probably due to the suppression of the production of proinflammatory cytokines in the pathological lesion.
关键词：TAS-3-124;tumor necrosis factor (TNF)-α;interleukin (IL)-1β;IL-6;collagen-induced arthritis (CIA);experimental autoimmune encephalomyelitis (EAE)