Amelioration of experimental autoimmune encephalomyelitis in lewis rats by FTY720 treatment
Amelioration of experimental autoimmune encephalomyelitis in lewis rats by FTY720 treatment
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DOI：
10.1124/jpet.102.045658
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发表时间：
2003-04-01
影响因子：
3.5
通讯作者：
Li, XK
中科院分区：
文献类型：
--
作者：
Fujino, M;Funeshima, N;Li, XK
实验性自身免疫性脑脊髓炎（EAE）是一种T细胞依赖性自身免疫疾病，它重现了多发性硬化症（MS）的炎症性脱髓鞘病理。我们通过给用髓鞘碱性蛋白和完全弗氏佐剂免疫的Lewis大鼠施用2 - 氨基 - [2 -（4 - 辛基苯基）乙基] - 1,3 - 丙二醇盐酸盐（FTY720），研究了其对EAE的免疫抑制功效和机制。FTY720治疗几乎完全保护大鼠免于患病。通过免疫组织化学检测，FTY720的保护作用与脊髓中T细胞受体染色的淋巴细胞数量大幅减少有关。通过逆转录聚合酶链反应评估，脊髓中Th1细胞因子白细胞介素（IL）-2、IL - 6和干扰素 - γ的mRNA表达也显著降低。此外，从FTY720治疗的大鼠脾脏中分离出的淋巴细胞被转移到未患病的受体大鼠中，通过降低疾病发病率和临床评分来对抗EAE的表现。这些结果表明，FTY720治疗的保护性抗炎作用在很大程度上是由于抑制了致脑炎T细胞反应和/或它们向中枢神经系统的迁移，并且可能是用于治疗MS患者的潜在候选药物。
Experimental autoimmune encephalomyelitis (EAE) is a T-cell-dependent autoimmune disease that reproduces the inflammatory demyelinating pathology of multiple sclerosis ( MS). We investigated the efficacy and mechanism of immunosuppression against EAE by administering 2-amino-[2-(4-octylphenyl) ethyl]-1,3-propanediol hydrochloride (FTY720) in Lewis rats immunized with myelin basic protein together with complete Freund's adjuvant. FTY720 treatment almost completely protected the rats against disease. The protection by FTY720 was associated with a dramatic reduction in the number of lymphocytes staining for T-cell receptors in the spinal cord as examined by immunohistochemistry. The mRNA expression of Th1 cytokines interleukin (IL)-2, IL-6, and interferon-gamma in the spinal cord was also reduced dramatically as assessed by reverse-transcription polymerase chain reaction. Furthermore, lymphocytes isolated from the spleen of FTY720-treated rats were transferred into naive recipient rats against EAE manifestation by reducing both disease incidence and clinical score. These results suggested that the protective anti-inflammatory effect of treatment with FTY720 was, to a large extent, due to the inhibition of encephalitogenic T-cell responses and/or their migration into the central nervous system and may be a potential candidate for use in treating patients with MS.