Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis
Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis
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DOI：
10.1016/j.cellimm.2005.11.002
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发表时间：
2005-10-01
影响因子：
4.3
通讯作者：
Gold, R
中科院分区：
文献类型：
--
作者：
Hofstetter, HH;Ibrahim, SM;Gold, R
实验性自身免疫性脑脊髓炎（EAE）被广泛认为是人类多发性硬化症的一种动物模型。大量研究已经对患有EAE的动物中存在的神经抗原特异性T细胞介导的细胞因子模式进行了研究。特别是所谓的Th1和Th2细胞因子的作用已经得到探讨。在最近的一项研究中……已经证明白细胞介素 - 23（IL - 23）而非白细胞介素 - 12（IL - 12）对于将发育中的免疫反应特性调节为促炎反应并导致EAE至关重要。白细胞介素 - 17（IL - 17）是一种关键的效应细胞因子，其产生由IL - 23特异性触发，并且已被证明在其他自身免疫性疾病和炎症病症中是一种重要的炎症介质。这促使我们研究IL - 17在EAE中的作用。通过酶联免疫斑点试验（ELISPOT）和逆转录聚合酶链反应（RT - PCR）分析表明，在急性和慢性EAE中，外周免疫器官和中枢神经系统（CNS）均显示出强烈的白细胞介素 - 17的抗原特异性产生。在急性EAE中用白细胞介素 - 17受体 - Fc蛋白对白细胞介素 - 17进行治疗性中和可改善临床症状。用单克隆抗体中和白细胞介素 - 17也可改善疾病进程。我们得出结论，白细胞介素 - 17作为EAE中的一种效应细胞因子在细胞因子网络中起着至关重要的作用。（c）2005爱思唯尔公司。保留所有权利。
Experimental autoimmune encephalomyelitis (EAE) is widely regarded as an animal model of the human disease multiple sclerosis. A multitude of studies has investigated the neuroantigen-specific T-cell mediated cytokine pattern present in animals with EAE. In particular, the role of the so-called Th1- and Th2-cytokines has been addressed. In a recent study.. it has been demonstrated that IL-23 rather than IL-12 is critical for modulating the character of the developing immune response towards a proinflammatory response and leading to EAE. IL-17 is a crucial effector cytokine, whose production is specifically triggered by IL-23, and it has been shown to be an essential,,g inflammatory mediator in other autoimmune diseases and inflammatory conditions. This led us to investigate the role of IL-17 in EAE. Strong antigen-specific production of IL-17 was demonstrated both in peripheral immune organs and in the CNS in acute and chronic EAE, as demonstrated by ELISPOT and RT-PCR analysis. Therapeutic neutralization of IL-17 with IL-17-receptor-Fc-protein in acute EAE ameliorated clinical symptoms. Neutralization of IL-17 with a monoclonal antibody also ameliorated the disease course. We conclude that IL-17 is crucially involved in the cytokine network as an effector cytokine in EAE. (c) 2005 Elsevier Inc. All rights reserved.