Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis

Masahiko Mihara1, Yoshiyuki Ohsugi2, Tadamitsu Kishimoto31Product Research Department, Chugai Pharmaceutical Co Ltd, Fuji-Gotemba Research Laboratories, Shizuoka, Japan; 2Chugai Pharmaceutical Co Ltd, Tokyo, Japan; 3Laboratory of Immunoregulation, Graduate School of Frontier Biosciences, Osaka Unive...

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Autores principales:	Masahiko Mihara, Yoshiyuki Ohsugi, Tadamitsu Kishimoto
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/12b0bcddd7234a7d999bf1771ed9a2a2
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spelling	oai:doaj.org-article:12b0bcddd7234a7d999bf1771ed9a2a22021-12-02T00:54:51ZTocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis1179-156Xhttps://doaj.org/article/12b0bcddd7234a7d999bf1771ed9a2a22011-02-01T00:00:00Zhttp://www.dovepress.com/tocilizumab-a-humanized-anti-interleukin-6-receptor-antibody-for-treat-a6493https://doaj.org/toc/1179-156XMasahiko Mihara1, Yoshiyuki Ohsugi2, Tadamitsu Kishimoto31Product Research Department, Chugai Pharmaceutical Co Ltd, Fuji-Gotemba Research Laboratories, Shizuoka, Japan; 2Chugai Pharmaceutical Co Ltd, Tokyo, Japan; 3Laboratory of Immunoregulation, Graduate School of Frontier Biosciences, Osaka University, Osaka, JapanAbstract: Interleukin (IL)-6 has a variety of biological functions. For example, it stimulates the production of acute-phase reactants (C-reactive protein and serum amyloid A) and hepcidin which interferes with iron recycling and absorption, causing iron-deficient anemia, and augments expression of vascular endothelial growth factor and receptor activator of nuclear factor-&kappa;B ligand in synovial cells, leading to neovascularization and osteoclast formation. IL-6 also acts on lymphocytes, not only on B cells to stimulate autoantibody production, but also on na&iuml;ve T helper cells to promote Th17 cell differentiation. Thus, an imbalance between T cell subsets possibly contributes to development of rheumatoid arthritis. Several clinical studies have demonstrated that a humanized anti-IL-6 receptor antibody, tocilizumab, improves clinical symptoms in rheumatoid arthritis. Tocilizumab prevented radiographic progression of joint destruction by inhibiting cartilage/bone resorption. Tocilizumab also improved hematological abnormalities, including hypergammaglobulinemia, high levels of autoantibodies, and elevation of erythrocyte sedimentation rate and acute-phase proteins. Importantly, tocilizumab improved quality of life by reducing systemic symptoms, including fatigue, anemia, anorexia, and fever. These findings have confirmed that hyperproduction of IL-6 is responsible for the above clinical symptoms, including joint destruction. Many patients treated with tocilizumab achieved clinical remission associated with decreased serum IL-6, suggesting that IL-6 enhances autoimmunity. Tocilizumab is a new therapeutic option for rheumatoid arthritis.Keywords: interleukin-6, tocilizumab, efficacy, safety, mode of action Masahiko MiharaYoshiyuki OhsugiTadamitsu KishimotoDove Medical PressarticleDiseases of the musculoskeletal systemRC925-935ENOpen Access Rheumatology: Research and Reviews, Vol 2011, Iss default, Pp 19-29 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the musculoskeletal system RC925-935
spellingShingle	Diseases of the musculoskeletal system RC925-935 Masahiko Mihara Yoshiyuki Ohsugi Tadamitsu Kishimoto Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis
description	Masahiko Mihara1, Yoshiyuki Ohsugi2, Tadamitsu Kishimoto31Product Research Department, Chugai Pharmaceutical Co Ltd, Fuji-Gotemba Research Laboratories, Shizuoka, Japan; 2Chugai Pharmaceutical Co Ltd, Tokyo, Japan; 3Laboratory of Immunoregulation, Graduate School of Frontier Biosciences, Osaka University, Osaka, JapanAbstract: Interleukin (IL)-6 has a variety of biological functions. For example, it stimulates the production of acute-phase reactants (C-reactive protein and serum amyloid A) and hepcidin which interferes with iron recycling and absorption, causing iron-deficient anemia, and augments expression of vascular endothelial growth factor and receptor activator of nuclear factor-&kappa;B ligand in synovial cells, leading to neovascularization and osteoclast formation. IL-6 also acts on lymphocytes, not only on B cells to stimulate autoantibody production, but also on na&iuml;ve T helper cells to promote Th17 cell differentiation. Thus, an imbalance between T cell subsets possibly contributes to development of rheumatoid arthritis. Several clinical studies have demonstrated that a humanized anti-IL-6 receptor antibody, tocilizumab, improves clinical symptoms in rheumatoid arthritis. Tocilizumab prevented radiographic progression of joint destruction by inhibiting cartilage/bone resorption. Tocilizumab also improved hematological abnormalities, including hypergammaglobulinemia, high levels of autoantibodies, and elevation of erythrocyte sedimentation rate and acute-phase proteins. Importantly, tocilizumab improved quality of life by reducing systemic symptoms, including fatigue, anemia, anorexia, and fever. These findings have confirmed that hyperproduction of IL-6 is responsible for the above clinical symptoms, including joint destruction. Many patients treated with tocilizumab achieved clinical remission associated with decreased serum IL-6, suggesting that IL-6 enhances autoimmunity. Tocilizumab is a new therapeutic option for rheumatoid arthritis.Keywords: interleukin-6, tocilizumab, efficacy, safety, mode of action
format	article
author	Masahiko Mihara Yoshiyuki Ohsugi Tadamitsu Kishimoto
author_facet	Masahiko Mihara Yoshiyuki Ohsugi Tadamitsu Kishimoto
author_sort	Masahiko Mihara
title	Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis
title_short	Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis
title_full	Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis
title_fullStr	Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis
title_full_unstemmed	Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis
title_sort	tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/12b0bcddd7234a7d999bf1771ed9a2a2
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Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis

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