alexa Iguratimod Synergizes with Methotrexate to Exert Anti-Inflammatory and Bone-Protective Effect and Block the Progression of Collagen-Induced Arthritis in Mices | Abstract
ISSN: 2167-0501

Biochemistry & Pharmacology: Open Access
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Research Article

Iguratimod Synergizes with Methotrexate to Exert Anti-Inflammatory and Bone-Protective Effect and Block the Progression of Collagen-Induced Arthritis in Mices

Qiong Luo1, Yang Sun1*, Biao Jin1, Wei Zheng1, Fenli Shao1, Nan Hang1, Yongqian Shu2, Xiaomin Li3, Yanhong Gu2* and Qiang Xu1*
1State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China
2Department of Oncology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China
3Department of Emergency, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu 222002, China
Corresponding Authors : Yang Sun
School of Life Sciences, Nanjing University
22 Hankou Road, Nanjing 210093 China
Tel: +86-25-835-976-20
E-mail: [email protected]
  Qiang Xu
School of Life Sciences, Nanjing University
22 Hankou Road, Nanjing 210093 China
Tel: +86-25-835-976-20
E-mail: [email protected]
  Yanhong Gu
Department of Oncology
The First Affiliated Hospital with Nanjing Medical University
300 Guangzhou Road, Nanjing 210029 China
Tel: +86-25-681-363-93
Fax: +86-25-837-100-40
E-mail: [email protected]
Received February 20, 2014; Accepted April 16, 2014; Published April 30, 2014
Citation: Luo Q, Sun Y, Jin B, Zheng W, Shao F, et al. (2014) Iguratimod Synergizes with Methotrexate to Exert Anti-Inflammatory and Bone-Protective Effect and Block the Progression of Collagen-Induced Arthritis in Mice. Biochem Pharmacol 3:135. doi:10.4172/2167-0501.1000135
Copyright: © 2014 Luo Q, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic synovial inflammation and disability.
The most widely used Disease-Modifying Antirheumatic Drug (DMARD) is methotrexate and it continues to be the gold
standard. However, the use of high-dose methotrexate is associated with severe adverse effects. Iguratimod, which is
currently used in clinics in China and Japan, is a novel oral DMARD for the treatment of RA. In this study, the effect
of combination of methotrexate and iguratimod on murine Collagen-Induced Arthritis (CIA) and its mechanism was
determined. Oral administration of iguratimod (3 mg/kg, 10 mg/kg) combined with methotrexate (1 mg/kg) potently
blocked CIA development and delayed its progression, which was stronger than iguratimod or methotrexate used alone.
Furthermore, infiltration of inflammatory cells into the synovium was remarkably inhibited by combination therapy and
importantly, no bone erosion and joint destructions were observed in combination therapy group. In addition, combined
administration of these two DMARDs suppressed production of cytokines (IL-17, IFN-γ, IL-6 and TNF-α) and antibodies
(IgG and IgG2b) in serum, as well as humoral and cellular responses in CIA mice. Consistent with its effects in vivo,
iguratimod combined with methotrexate significantly suppressed T and B cells responses in vitro. Taken together, our
findings suggest that combination treatment with iguratimod and methotrexate should be an intriguing and preferable
therapeutic strategy for treating RA.

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