Musculoskeletal Research Group, Institute of Cellular Medicine, 4(th) Floor Cookson Building, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom. Steven.O'
Cytokine Growth Factor Rev. 2012 Jun;23(3):99-107. doi: 10.1016/j.cytogfr.2012.04.003. Epub 2012 May 5.
Interleukin-6 is a classic pro-inflammatory cytokine needed to mount an effective immune response. It is secreted by a wide array of cell types, however, its target cells are more restricted, due to the fact that very few cells, except lymphocytes and hepatocytes, express the functional membrane IL-6 receptor. This therefore limits the amount of cells that can respond to IL-6. Transsignalling, the shedding of the membrane bound form of the IL-6 receptor (sIL-6R) into the local microenvironment, greatly increases the range of cells that can respond e.g. as part of a wound healing response necessary to restore the homeostatic balance. Therefore, tight regulation of IL-6 signalling must occur to stop an inappropriate wound healing response occurring. This review focusses on the role of IL-6 in inflammation and fibrosing conditions, with a particular emphasis on systemic sclerosis (SSc), a chronic autoimmune disease in which a classical hallmark of fibrosis occurs. This fibrosis, in particular the skin and internal organs, leads to contractures and internal organ failure respectively with potential fatal consequences. In this review we will discuss the biology of IL-6 in the context of fibrosing conditions such as SSc and argue why molecular targeting of IL-6 is a promising therapeutic target.
白细胞介素 6 是一种经典的促炎细胞因子，是引发有效免疫反应所必需的。它由多种细胞类型分泌，但由于只有极少数细胞（淋巴细胞和肝细胞除外）表达功能性膜白细胞介素 6 受体，其靶细胞受到限制。因此，能够对白细胞介素 6 做出反应的细胞数量有限。转信号，即将膜结合形式的白细胞介素 6 受体 (sIL-6R) 脱落到局部微环境中，极大地增加了能够做出反应的细胞范围，例如在伤口愈合反应中，这是恢复体内平衡所必需的。因此，必须对白细胞介素 6 信号进行严格的调节，以防止发生不适当的伤口愈合反应。这篇综述重点介绍了白细胞介素 6 在炎症和纤维化疾病中的作用，特别是全身性硬皮病 (SSc)，这是一种慢性自身免疫性疾病，其中发生了纤维化的经典特征。这种纤维化，特别是皮肤和内部器官，分别导致挛缩和内部器官衰竭，具有潜在的致命后果。在这篇综述中，我们将讨论白细胞介素 6 在纤维化疾病（如 SSc）中的生物学，并论证为什么靶向白细胞介素 6 的分子是一种有前途的治疗靶点。
