ORIGINAL ARTICLE

Imatinib mesylate both prevents and treats the arthritis induced by type II collagen antibody in mice

Authors

Kensuke Koyama^1,2, Kyosuke Hatsushika¹, Takashi Ando¹, Michitomo Sakuma¹, Masanori Wako¹, Ryohei Kato³, Hirotaka Haro², Hajime Sugiyama², Yoshiki Hamada², Hideoki Ogawa⁴ and Atsuhito Nakao^1,4

1. Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
2. Department of Orthopaedic Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan
3. Department of Human Pathology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
4. Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan

Received:

08 February 2007

Accepted:

01 May 2007

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Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is associated with joint destruction. Imatinib mesylate (imatinib) is an inhibitor that specifically targets a set of protein tyrosine kinase, such as abl, c-kit, and platelet-derived growth factor receptor (PDGFR) and it is widely used to treat chronic myeloid leukemia (CML). The purpose of the present study is to determine whether imatinib can provide benefit in the arthritis induced by anti-collagen type II antibody (CAIA) in mice, a model that provides an opportunity to study the effector inflammatory phase of arthritis without involving the priming phase of the immune responses. Mice treated with intraperitoneal administration of imatinib (1 or 10mg/kg) prior to the development of CAIA displayed significant reductions in the severity of CAIA as assessed by arthritis score, histology, and synovial PDGF and vascular endothelial growth factor expression. In addition, treatment of the mice that had developed CAIA with intraperitoneal administration of imatinib (1 or 10mg/kg) inhibited the progression of arthritis as assessed by those parameters. These results suggest that imatinib prevents and treats CAIA. Imatinib may thus have both a preventive and therapeutic potential for the joint inflammation at the effector stage of RA.

Key words

Anti-collagen type II antibody-induced arthritis (CAIA) - Imatinib mesylate - Rheumatoid arthritis