Interleukin 6 and Rheumatoid Arthritis

BioMed Research International - Tập 2014 - Trang 1-12 - 2014
Yūji Yoshida1, Toshio Tanaka2,3
1Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
2Department of Clinical Application of Biologics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita City, Osaka 565-0871, Japan
3Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan

Tóm tắt

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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Tài liệu tham khảo

2011, The New England Journal of Medicine, 365, 2205, 10.1056/NEJMra1004965

10.1136/ard.2009.123919

10.1586/eci.10.70

10.1146/annurev-pharmtox-010611-134715

2013, Rheumatology: Current Research, 3

1982, The Journal of Immunology, 128, 1296, 10.4049/jimmunol.128.3.1296

1985, Annual Review of Immunology, 3, 133, 10.1146/annurev.iy.03.040185.001025

1986, Nature, 324, 73, 10.1038/324073a0

1992, Proceedings of the National Academy of Sciences of the United States of America, 89, 232, 10.1073/pnas.89.1.232

1987, Proceedings of the National Academy of Sciences of the United States of America, 84, 7251, 10.1073/pnas.84.20.7251

1990, Biochemical Journal, 265, 621, 10.1042/bj2650621

1990, Immunology Today, 11, 443

1993, Advances in Immunology, 54, 1, 10.1016/S0065-2776(08)60532-5

10.1146/annurev.immunol.23.021704.115806

1988, Science, 241, 825, 10.1126/science.3136546

1992, Science, 258, 593, 10.1126/science.1411569

1989, Cell, 58, 573, 10.1016/0092-8674(89)90438-8

10.1016/0092-8674(90)90411-7

1994, Science, 263, 89, 10.1126/science.8272872

1994, Science, 263, 92, 10.1126/science.8272873

2012, International Journal of Biological Sciences, 8, 1237, 10.7150/ijbs.4989

1994, Cell, 77, 63, 10.1016/0092-8674(94)90235-6

1995, Science, 267, 1349, 10.1126/science.7871433

1996, The Journal of Biological Chemistry, 271, 12991, 10.1074/jbc.271.22.12991

10.1074/jbc.272.24.15135

1999, Blood, 93, 1934, 10.1182/blood.V93.6.1934.406k05_1934_1941

10.1038/nrd1902

10.1016/j.ejphar.2010.03.030

1989, Proceedings of the National Academy of Sciences of the United States of America, 86, 7547, 10.1073/pnas.86.19.7547

10.1084/jem.185.3.461

10.1146/annurev.immunol.021908.132710

10.1002/eji.201040391

10.1038/nature05969

10.1084/jem.20072057

10.1084/jem.20081571

10.1007/s00296-009-0953-0

1996, Journal of Bone and Mineral Research, 11, 88, 10.1002/jbmr.5650110113

2002, The Journal of Immunology, 169, 3353, 10.4049/jimmunol.169.6.3353

10.1016/j.cyto.2010.03.017

10.1002/art.11143

10.1172/JCI200420945

1989, Blood, 74, 1241, 10.1182/blood.V74.4.1241.1241

1988, European Journal of Immunology, 18, 1797, 10.1002/eji.1830181122

1991, European Journal of Clinical Investigation, 21, 479, 10.1111/j.1365-2362.1991.tb01398.x

1992, The Journal of Rheumatology, 19, 22

1993, Annals of the Rheumatic Diseases, 52, 232, 10.1136/ard.52.3.232

1997, British Journal of Rheumatology, 36, 1298, 10.1093/rheumatology/36.12.1298

10.1007/s10165-013-0894-z

10.1084/jem.187.4.461

1999, Arthritis & Rheumatism, 42, 1635, 10.1002/1529-0131(199908)42:8<1635::AID-ANR11>3.0.CO;2-Q

1998, Arthritis & Rheumatism, 41, 2117, 10.1002/1529-0131(199812)41:12<2117::AID-ART6>3.0.CO;2-P

10.1002/art.24126

10.1073/pnas.95.14.8222

10.1002/art.21537

10.1038/nature02119

10.1172/JCI200421795

10.1084/jem.20062259

1993, Cancer Research, 53, 851

2000, Blood, 95, 56, 10.1182/blood.V95.1.56

10.1182/blood-2004-12-4602

10.1002/art.10623

2003, The Journal of Rheumatology, 30, 1426

10.1002/art.22033

10.1016/S0140-6736(08)60453-5

10.1002/art.23940

10.1136/ard.2008.092932

10.1002/art.30158

10.1136/ard.2008.105197

10.1136/ard.2006.068064

10.1007/s10165-008-0125-1

10.1007/s10165-010-0366-7

10.1093/rheumatology/ker221

10.1136/annrheumdis-2011-201282

2013, The Lancet, 381, 1541, 10.1016/S0140-6736(13)60250-0

10.1136/annrheumdis-2013-203485

10.3899/jrheum.100717

10.1002/acr.22110

10.1136/annrheumdis-2013-203523

10.1186/ar3455

10.1136/ard.2011.151092

2011, Cochrane Database of Systematic Reviews, 2

2013, The Journal of Rheumatology, 40, 768, 10.3899/jrheum.120687

10.1007/s10067-011-1827-x

10.1136/ard.2008.104844

2012, Annals of the Rheumatic Diseases, 71, 60, 10.1136/annrheumdis-2011-200596

2012, Annals of the Rheumatic Diseases, 71, 188

10.1007/s00296-011-2021-9

2011, Clinical and Experimental Rheumatology, 29, 921

10.1016/j.semarthrit.2013.07.008

2013, Immunotherapy, 5, 695, 10.2217/imt.13.47

2012, Arthritis & Rheumatism, 64, 2499, 10.1002/art.34477

2013, Clinical & Experimental Immunology, 171, 237, 10.1111/cei.12017

2013, International Journal of Biological Sciences, 9, 279, 10.7150/ijbs.5996

10.1186/ar4100

1998, The Journal of Clinical Investigation, 102, 1369, 10.1172/JCI2629

10.1007/s00011-012-0455-5

2013, Inflammation and Regeneration, 33, 54, 10.2492/inflammregen.33.054

10.1038/nature07924

10.1038/ni.2137

2013, Proceedings of the National Academy of Sciences of the United States of America, 110, 9409, 10.1073/pnas.1307419110