IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer

被引:487
作者
Neurath, Markus F. [1 ]
Finotto, Susetta [1 ]
机构
[1] Univ Erlangen Nurnberg, Med Clin 1, D-91054 Erlangen, Germany
关键词
IL-6; Cytokines; TH17; cells; T cell differentiation; Regulatory and effector T cells; Inflammatory bowel disease; Asthma; Rheumatoid arthritis; Cancer; CHRONIC INTESTINAL INFLAMMATION; CELL-MEDIATED COLITIS; NECROSIS-FACTOR-ALPHA; CD4(+) T-CELLS; INTERLEUKIN-6; IL-6; BOWEL-DISEASE; TGF-BETA; IL-6-DEFICIENT MICE; RHEUMATOID-ARTHRITIS; CUTTING EDGE;
D O I
10.1016/j.cytogfr.2011.02.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
IL-6 activates various cell types carrying the membrane bound IL-6R (classical IL-6 signaling) as well as IL-6R(-) gp130(+) cells via the soluble IL-6R (IL-6 trans-signaling). IL-6 signaling plays a pivotal role in controlling the differentiation and activation of T lymphocytes by inducing the Jak/STAT-3 and the Ras/Erk/C/EBP pathways. In particular, IL-6 modulates the resistance of T cells against apoptosis, induces activation of T helper cells and controls the balance between regulatory T cells and Th17 cells. Importantly, recent findings suggest that blockade of IL-6 signaling is effective in treating experimental models of autoimmune and chronic inflammatory diseases such as inflammatory bowel diseases, diabetes, multiple sclerosis, asthma and rheumatoid arthritis as well as models of inflammation-associated cancer. Thus, anti-IL-6/anti-IL-6R strategies emerge as promising novel approaches for therapy of inflammatory diseases in humans. In this review article, we discuss the latest findings on the role of IL-6 in experimental models of autoimmunity and cancer, as well as clinical perspectives. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:83 / 89
页数:7
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