title: Interleukin-6: a new therapeutic target in systemic sclerosis?
abstract: Interleukin-6 (IL-6) is a classic pro-inflammatory cytokine critical in mounting an effective immune response. It is secreted by a wide array of cell types; however, its effector cells are more restricted, owing to the fact that very few cells, except lymphocytes and hepatocytes, express the functional membrane IL-6 receptor thus reducing the number of IL-6-responsive cells. Trans-signalling, the shedding of the membrane-bound form of the IL-6 receptor into the local microenvironment, greatly increases the range of cells that can respond. IL-6 has been demonstrated to have a pivotal role in the pathogenesis of rheumatoid arthritis, Castleman's disease and Crohn's disease exemplified by the use of an anti-IL-6 biological therapy. However, IL-6 is also associated with the autoimmune disease systemic sclerosis (SSc) and has been shown to be directly fibrotic. Elevated levels of IL-6 are found in SSc patients and this correlates with skin thickness, suggesting a causal effect. This review focuses on the role of IL-6 in SSc, a chronic autoimmune disease with fibrosis. In particular, we will examine the evidence base of the role of IL-6 in fibrosis in this condition, especially the downstream effector pathways. We will then argue why molecular targeting of IL-6 is a promising therapeutic target in this fibrosing disease.
authors.affiliation: Musculoskeletal Research Group, Institute of Cellular Medicine , Newcastle upon Tyne, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: O'Reilly
authors.affiliation: Musculoskeletal Research Group, Institute of Cellular Medicine , Newcastle upon Tyne, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Cant
authors.affiliation: Musculoskeletal Research Group, Institute of Cellular Medicine , Newcastle upon Tyne, UK.
authors.forename: Marzena
authors.initials: M
authors.lastname: Ciechomska
authors.affiliation: Musculoskeletal Research Group, Institute of Cellular Medicine , Newcastle upon Tyne, UK.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
keywords: Th17; fibrosis; interleukin-6; interleukin-6 signalling; systemic sclerosis