Interleukin 6 and Rheumatoid Arthritis

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2014 Feb 14

PMID 24524085

Citations 84

Authors

Yuji Yoshida

Toshio Tanaka

Affiliations

Soon will be listed here.

Abstract

Interleukin-6 (IL-6) is a representative cytokine featuring pleiotropic activity and redundancy. A transient synthesis of IL-6 contributes to host defense against infectious agents and tissue injuries by inducing acute phase reactions and immunological and hematopoietic responses. However, uncontrolled persistent production of IL-6 may lead to the development of several immune-mediated diseases. Rheumatoid arthritis (RA) is a chronic disease with joint and systemic inflammation resulting from immunological abnormalities and it has been found that IL-6 plays a key role in the development of this disease. Clinical trials in various parts of the world of tocilizumab, a humanized anti-IL-6 receptor antibody, have proved its efficacy and tolerable safety either as monotherapy or in combination with disease-modifying antirheumatic drugs. As a result, it is currently used as a first-line biologic for the treatment of moderate-to-severe RA in more than 100 countries. Clarification of the mechanism(s) through which tocilizumab exerts its effect on RA and of the reason(s) why IL-6 is continuously produced in RA can be expected to lead to the best use of this agent for RA patients and aid in investigations into the pathogenesis of RA.

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References

Suematsu S, Matsuda T, Aozasa K, Akira S, Nakano N, Ohno S . IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci U S A. 1989; 86(19):7547-51. PMC: 298102. DOI: 10.1073/pnas.86.19.7547. View

Kishimoto T, Akira S, Taga T . Interleukin-6 and its receptor: a paradigm for cytokines. Science. 1992; 258(5082):593-7. DOI: 10.1126/science.1411569. View

Pesce B, Soto L, Sabugo F, Wurmann P, Cuchacovich M, Lopez M . Effect of interleukin-6 receptor blockade on the balance between regulatory T cells and T helper type 17 cells in rheumatoid arthritis patients. Clin Exp Immunol. 2013; 171(3):237-42. PMC: 3569529. DOI: 10.1111/cei.12017. View

Stahl N, Farruggella T, Boulton T, Zhong Z, Darnell Jr J, Yancopoulos G . Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors. Science. 1995; 267(5202):1349-53. DOI: 10.1126/science.7871433. View

Yamanaka H, Tanaka Y, Inoue E, Hoshi D, Momohara S, Hanami K . Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study). Mod Rheumatol. 2010; 21(2):122-33. PMC: 3071926. DOI: 10.1007/s10165-010-0366-7. View

Terpos E, Fragiadaki K, Konsta M, Bratengeier C, Papatheodorou A, Sfikakis P . Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in women with rheumatoid arthritis. Clin Exp Rheumatol. 2011; 29(6):921-5. View

Hashizume M, Yoshida H, Koike N, Suzuki M, Mihara M . Overproduced interleukin 6 decreases blood lipid levels via upregulation of very-low-density lipoprotein receptor. Ann Rheum Dis. 2009; 69(4):741-6. DOI: 10.1136/ard.2008.104844. View

Dougados M, Kissel K, Sheeran T, Tak P, Conaghan P, Martin Mola E . Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis. 2012; 72(1):43-50. PMC: 3551223. DOI: 10.1136/annrheumdis-2011-201282. View

Genovese M, Rubbert-Roth A, Smolen J, Kremer J, Khraishi M, Gomez-Reino J . Longterm safety and efficacy of tocilizumab in patients with rheumatoid arthritis: a cumulative analysis of up to 4.6 years of exposure. J Rheumatol. 2013; 40(6):768-80. DOI: 10.3899/jrheum.120687. View

10.

Hirano T, Matsuda T, Turner M, Miyasaka N, Buchan G, Tang B . Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol. 1988; 18(11):1797-801. DOI: 10.1002/eji.1830181122. View

11.

Rose-John S . IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int J Biol Sci. 2012; 8(9):1237-47. PMC: 3491447. DOI: 10.7150/ijbs.4989. View

12.

Nishimoto N, Amano K, Hirabayashi Y, Horiuchi T, Ishii T, Iwahashi M . Drug free REmission/low disease activity after cessation of tocilizumab (Actemra) Monotherapy (DREAM) study. Mod Rheumatol. 2013; 24(1):17-25. DOI: 10.3109/14397595.2013.854079. View

13.

Tanaka T . Can IL-6 blockade rectify imbalance between Tregs and Th17 cells?. Immunotherapy. 2013; 5(7):695-7. DOI: 10.2217/imt.13.47. View

14.

Gabay C, Emery P, van Vollenhoven R, Dikranian A, Alten R, Pavelka K . Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet. 2013; 381(9877):1541-50. DOI: 10.1016/S0140-6736(13)60250-0. View

15.

Heinrich P, Castell J, Andus T . Interleukin-6 and the acute phase response. Biochem J. 1990; 265(3):621-36. PMC: 1133681. DOI: 10.1042/bj2650621. View

16.

Smolen J, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E . Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008; 371(9617):987-97. DOI: 10.1016/S0140-6736(08)60453-5. View

17.

Ohshima S, Saeki Y, Mima T, Sasai M, Nishioka K, Nomura S . Interleukin 6 plays a key role in the development of antigen-induced arthritis. Proc Natl Acad Sci U S A. 1998; 95(14):8222-6. PMC: 20957. DOI: 10.1073/pnas.95.14.8222. View

18.

Burmester G, Rubbert-Roth A, Cantagrel A, Hall S, Leszczynski P, Feldman D . A randomised, double-blind, parallel-group study of the safety and efficacy of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional disease-modifying antirheumatic drugs in patients with moderate to severe.... Ann Rheum Dis. 2013; 73(1):69-74. PMC: 3888614. DOI: 10.1136/annrheumdis-2013-203523. View

19.

Schiff M, Kremer J, Jahreis A, Vernon E, Isaacs J, van Vollenhoven R . Integrated safety in tocilizumab clinical trials. Arthritis Res Ther. 2011; 13(5):R141. PMC: 3308069. DOI: 10.1186/ar3455. View

20.

Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H . Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987; 84(20):7251-5. PMC: 299269. DOI: 10.1073/pnas.84.20.7251. View