Recent advances in neutralizing the IL-6 pathway in arthritis

Charles J MalemudDivision of Rheumatic Diseases, Case Western Reserve University, School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USAAbstract: Recent advances in understanding the mechanism(s) of how IL-6 trans-signaling regulates immune cell function and promotes i...

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Autor principal:	Charles J Malemud
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2009
Materias:	Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/b7c2345493cb47778126e13428d3e1db
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spelling	oai:doaj.org-article:b7c2345493cb47778126e13428d3e1db2021-12-02T08:47:47ZRecent advances in neutralizing the IL-6 pathway in arthritis1179-156Xhttps://doaj.org/article/b7c2345493cb47778126e13428d3e1db2009-10-01T00:00:00Zhttp://www.dovepress.com/recent-advances-in-neutralizing-the-il-6-pathway-in-arthritis-a3610https://doaj.org/toc/1179-156XCharles J MalemudDivision of Rheumatic Diseases, Case Western Reserve University, School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USAAbstract: Recent advances in understanding the mechanism(s) of how IL-6 trans-signaling regulates immune cell function and promotes inflammation in autoimmune arthritis are critically reviewed. Serum and/or synovial fluid (SF) IL-6 is markedly elevated in adult and juvenile rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and osteoarthritis (OA). IL-6, in concert with IL-17, determines the fate of CD4+ lymphocytes and therefore TH17 cell differentiation. IL-6 also plays a critical role in modulating B-lymphocyte activity. The recognition that IL-6 trans-signaling regulates inflammation resulted in the development of tocilizumab, a fully humanized monoclonal antibody that neutralizes the biological activity of the IL-6-receptor (IL-6R). Significant clinical benefit was demonstrated as well as reduced serum IL-6 levels with suppression of X-ray progression of disease in several clinical trials in which juvenile or adult RA patients were treated with tocilizumab monotherapy or tocilizumab plus methotrexate. However, levels of serum and/or SF IL-6 cytokine protein superfamily members, adiponectin, oncostatin M, pre-B-cell colony enhancing factor/visfatin and leukemia inhibitory factor are also elevated in RA. Additional studies will be required to determine if anti-IL-6 trans-signaling inhibition strategies with tocilizumab or recombinant soluble IL-6R reduce the level of these cytokines.Keywords: interleukin-6, interleukin-6/interleukin-6 receptor/glycoprotein 130, JAK/STAT pathway, SAP/MAPK pathway, osteoarthritis, rheumatoid arthritis Charles J MalemudDove Medical PressarticleDiseases of the musculoskeletal systemRC925-935ENOpen Access Rheumatology: Research and Reviews, Vol 2009, Iss default, Pp 133-150 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the musculoskeletal system RC925-935
spellingShingle	Diseases of the musculoskeletal system RC925-935 Charles J Malemud Recent advances in neutralizing the IL-6 pathway in arthritis
description	Charles J MalemudDivision of Rheumatic Diseases, Case Western Reserve University, School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USAAbstract: Recent advances in understanding the mechanism(s) of how IL-6 trans-signaling regulates immune cell function and promotes inflammation in autoimmune arthritis are critically reviewed. Serum and/or synovial fluid (SF) IL-6 is markedly elevated in adult and juvenile rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and osteoarthritis (OA). IL-6, in concert with IL-17, determines the fate of CD4+ lymphocytes and therefore TH17 cell differentiation. IL-6 also plays a critical role in modulating B-lymphocyte activity. The recognition that IL-6 trans-signaling regulates inflammation resulted in the development of tocilizumab, a fully humanized monoclonal antibody that neutralizes the biological activity of the IL-6-receptor (IL-6R). Significant clinical benefit was demonstrated as well as reduced serum IL-6 levels with suppression of X-ray progression of disease in several clinical trials in which juvenile or adult RA patients were treated with tocilizumab monotherapy or tocilizumab plus methotrexate. However, levels of serum and/or SF IL-6 cytokine protein superfamily members, adiponectin, oncostatin M, pre-B-cell colony enhancing factor/visfatin and leukemia inhibitory factor are also elevated in RA. Additional studies will be required to determine if anti-IL-6 trans-signaling inhibition strategies with tocilizumab or recombinant soluble IL-6R reduce the level of these cytokines.Keywords: interleukin-6, interleukin-6/interleukin-6 receptor/glycoprotein 130, JAK/STAT pathway, SAP/MAPK pathway, osteoarthritis, rheumatoid arthritis
format	article
author	Charles J Malemud
author_facet	Charles J Malemud
author_sort	Charles J Malemud
title	Recent advances in neutralizing the IL-6 pathway in arthritis
title_short	Recent advances in neutralizing the IL-6 pathway in arthritis
title_full	Recent advances in neutralizing the IL-6 pathway in arthritis
title_fullStr	Recent advances in neutralizing the IL-6 pathway in arthritis
title_full_unstemmed	Recent advances in neutralizing the IL-6 pathway in arthritis
title_sort	recent advances in neutralizing the il-6 pathway in arthritis
publisher	Dove Medical Press
publishDate	2009
url	https://doaj.org/article/b7c2345493cb47778126e13428d3e1db
work_keys_str_mv	AT charlesjmalemud recentadvancesinneutralizingtheil6pathwayinarthritis
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Recent advances in neutralizing the IL-6 pathway in arthritis

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