Effects of FTY720, a novel immunosuppressant, on experimental autoimmune uveoretinitis in rats
Effects of FTY720, a novel immunosuppressant, on experimental autoimmune uveoretinitis in rats
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DOI：
10.1006/exer.1999.0777
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发表时间：
2000-01-01
影响因子：
3.4
通讯作者：
Mochizuki, M
中科院分区：
文献类型：
--
作者：
Kurose, S;Ikeda, E;Mochizuki, M
FTY720是一种新型免疫抑制剂，通过对从虫草棒束孢（Isaria sinclairii）发酵液中分离出的ISP - I进行结构修饰而获得。本研究在大鼠实验性自身免疫性葡萄膜视网膜炎（EAU）中对其免疫抑制特性进行了研究。Lewis大鼠用S - 抗原免疫，并在免疫后用FTY720（0.03、0.06、0.1 mg·kg⁻¹·d⁻¹）或蒸馏水治疗16天。临床和组织学检查表明，FTY720以剂量依赖的方式抑制EAU的发病率和严重程度。该药物显著抑制了抗S - 抗原的血清抗体水平以及抗原特异性淋巴细胞增殖。FTY720治疗可使外周淋巴细胞数量显著减少，但对中性粒细胞无影响。从EAU发病当天开始给药时，FTY720也可抑制EAU的严重程度。这些结果表明，FTY720对大鼠EAU具有强烈的免疫抑制作用，可能是治疗自身免疫性葡萄膜炎患者的潜在候选药物。（C）2000学术出版社
The immunosuppressive properties of FTY720, a novel immunosuppressant obtained by structural modification of ISP-I isolated from the fermentation broth of Isaria sinclairii, were studied in experimental autoimmune uveoretinitis (EAU) in rats. Lewis rats were immunized with S-antigen and treated with FTY720 (0.03, 0.06, 0.1 mg kg(-1) day(-1)) or distilled water for 16 days after the immunization. FTY720 suppressed the incidence and intensity of EAU in a dose-dependent manner as demonstrated by clinical and histological examinations. The drug significantly suppressed the serum levels of antibodies to Santigen and antigens-specific lymphocyte proliferation. The number of peripheral lymphocytes, but not neutrophils, was markedly reduced by FTY720 treatment. FTY720 also suppressed the intensity of EAU when it was given from the day of EAU onset. These results indicate that FTY720 has intense immunosuppressive effects on EAU in rats and may be a potential candidate for use in the treatment of patients with autoimmune uveitis. (C) 2000 Academic Press.