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

• Published in: Cytokine & growth factor reviews Vol. 22; no. 2; pp. 83 - 89
• Main Authors: Neurath, Markus F, Finotto, Susetta
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2011
• Subjects: Advanced Basic Science; Animals; Apoptosis - drug effects; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Asthma; Asthma - immunology; Autoimmunity - drug effects; Cancer; Cell Differentiation - drug effects; Colitis - complications; Colonic Neoplasms - complications; Colonic Neoplasms - immunology; Cytokines; Diabetes Mellitus, Type 1 - drug therapy; Encephalomyelitis, Autoimmune, Experimental - immunology; Humans; IL-6; Inflammation - immunology; Inflammatory bowel disease; Inflammatory Bowel Diseases - immunology; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - immunology; Multiple Sclerosis - immunology; Receptors, Interleukin-6 - physiology; Regulatory and effector T cells; Rheumatoid arthritis; Signal Transduction - immunology; T cell differentiation; T-Lymphocytes - immunology; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Regulatory - immunology; TH17 cells; Inflammatory bowel disease; Cytokines; Regulatory and effector T cells; T cell differentiation; Rheumatoid arthritis; TH17 cells; IL-6; Asthma; Cancer
• ISSN: 1359-6101; 1879-0305
• DOI: 10.1016/j.cytogfr.2011.02.003

Abstract 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.