Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer

• Published in: Nature reviews. Immunology Vol. 18; no. 12; pp. 773 - 789
• Main Authors: Jones, Simon A., Jenkins, Brendan J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2018; Nature Publishing Group
• Subjects: 631/250/127; 631/250/127/1214; 631/250/127/1217; 631/250/580; Adaptive Immunity - immunology; Autoimmune Diseases - drug therapy; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Autoimmunity; Biomedical and Life Sciences; Biomedicine; Cancer; Chronic diseases; Chronic infection; Ciliary neurotrophic factor; Cytokine Receptor gp130 - metabolism; Cytokines; Development and progression; Family relations; Genetic aspects; Health aspects; Homeostasis; Humans; Immunity, Innate - immunology; Immunology; Immunosuppressive agents; Inflammation; Inflammation - drug therapy; Inflammation - immunology; Inflammation - pathology; Inflammatory diseases; Interleukin 11; Interleukin 27; Interleukin 6; Interleukin-6 - metabolism; Intracellular signalling; Leukemia; Leukemia inhibitory factor; Medical schools; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - pathology; Oncostatin M; Physiological aspects; Review Article; Signal transduction; Signal Transduction - immunology; Australia; United Kingdom
• ISSN: 1474-1733; 1474-1741
• DOI: 10.1038/s41577-018-0066-7

The IL-6 family of cytokines consists of IL-6, IL-11, IL-27, IL-31, oncostatin M (OSM), leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin 1 (CT-1) and cardiotrophin-like cytokine factor 1 (CLCF1). Membership of this cytokine family is defined by usage of common β-receptor signalling subunits, which activate various intracellular signalling pathways. Each IL-6 family member elicits responses essential to the physiological control of immune homeostasis, haematopoiesis, inflammation, development and metabolism. Accordingly, distortion of these cytokine activities often promotes chronic disease and cancer; the pathological importance of this is exemplified by the successful treatment of certain autoimmune conditions with drugs that target the IL-6 pathway. Here, we discuss the emerging roles for IL-6 family members in infection, chronic inflammation, autoimmunity and cancer and review therapeutic strategies designed to manipulate these cytokines in disease. This Review considers the key roles of the IL-6 cytokine family in regulating innate and adaptive immunity, as well as other physiological responses. The authors highlight the potential of targeting IL-6 family members to treat inflammatory diseases and cancer.