title: IL-6 biology: implications for clinical targeting in rheumatic disease.
abstract: IL-6 has been linked to numerous diseases associated with inflammation, including rheumatoid arthritis, inflammatory bowel disease, vasculitis and several types of cancer. Moreover, IL-6 is important in the induction of hepatic acute-phase proteins for the trafficking of acute and chronic inflammatory cells, the differentiation of adaptive T-cell responses, and tissue regeneration and homeostatic regulation. Studies have investigated IL-6 biology using cell-bound IL-6 receptors expressed predominantly on hepatocytes and certain haematopoietic cells versus activation mediated by IL-6 and soluble IL-6 receptors via a second protein, gp130, which is expressed throughout the body. Advances in this research elucidating the differential effects of IL-6 activation provide important insights into the role of IL-6 in health and disease, as well as its potential as a therapeutic target. Knowledge of the basic biology of IL-6 and its signalling pathways can better inform both the research agenda for IL-6-based targeted therapies as well as the clinical use of strategies affecting IL-6-mediated inflammation. This Review covers novel, emerging aspects of the biology of IL-6, which might lead to more specific blockade of IL-6 signalling without compromising the protective function of this cytokine in the body's defence against infections.
authors.affiliation: Department of Rheumatic and Immunologic Diseases, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Calabrese
authors.affiliation: Department of Biochemistry, University of Kiel, Olshausenstrasse 40, Kiel 24098, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
mesh_terms: D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D012216:Rheumatic Diseases / Q000188:drug therapy / Q000209:etiology*; D015398:Signal Transduction; D000093242:Interleukin-6 Inhibitors
chemical_list: D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors