Interleukin-6: a new therapeutic target in systemic sclerosis?
Interleukin-6: a new therapeutic target in systemic sclerosis?
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DOI：
10.1038/cti.2013.2
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发表时间：
2013-04
影响因子：
5.8
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中科院分区：
文献类型：
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白介素6(IL-6)是一种经典的促炎细胞因子，在启动有效的免疫反应中起关键作用。它由多种细胞类型分泌；然而，它的效应细胞受到更多的限制，因为除了淋巴细胞和肝细胞外，很少有细胞表达功能膜IL-6受体，从而减少了IL-6反应细胞的数量。反式信号传递，即IL-6受体的膜结合形式进入局部微环境，极大地增加了细胞的反应范围。IL-6已经被证明在类风湿性关节炎、Castleman病和克罗恩病的发病机制中起着关键作用，抗IL-6生物疗法的使用就是例证。然而，IL-6也与自身免疫性疾病系统性硬化症(SSC)有关，并已被证明是直接纤维化的。在SSC患者中发现IL-6水平升高，这与皮肤厚度相关，提示存在因果关系。本文就IL-6在慢性自身免疫性疾病SSC中的作用进行综述。特别是，我们将检查在这种情况下IL-6在纤维化中作用的证据基础，特别是下游效应通路。然后我们将讨论为什么IL-6的分子靶向是这种纤维化疾病的一个有前途的治疗靶点。
Interleukin-6 (IL-6) is a classic pro-inflammatory cytokine critical in mounting an effective immune response. It is secreted by a wide array of cell types; however, its effector cells are more restricted, owing to the fact that very few cells, except lymphocytes and hepatocytes, express the functional membrane IL-6 receptor thus reducing the number of IL-6-responsive cells. Trans-signalling, the shedding of the membrane-bound form of the IL-6 receptor into the local microenvironment, greatly increases the range of cells that can respond. IL-6 has been demonstrated to have a pivotal role in the pathogenesis of rheumatoid arthritis, Castleman's disease and Crohn's disease exemplified by the use of an anti-IL-6 biological therapy. However, IL-6 is also associated with the autoimmune disease systemic sclerosis (SSc) and has been shown to be directly fibrotic. Elevated levels of IL-6 are found in SSc patients and this correlates with skin thickness, suggesting a causal effect. This review focuses on the role of IL-6 in SSc, a chronic autoimmune disease with fibrosis. In particular, we will examine the evidence base of the role of IL-6 in fibrosis in this condition, especially the downstream effector pathways. We will then argue why molecular targeting of IL-6 is a promising therapeutic target in this fibrosing disease.