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THU0061 The Effect of Anti-IL-6 Receptor Antibody on Cartilage Destruction in a Mouse Model of Collagen-Induced Arthritis
  1. M. Suzuki,
  2. Y. Bi,
  3. H. Yoshida,
  4. K. Tanaka,
  5. M. Hashizume,
  6. Y. Matsumoto
  1. Product Research Dept., CHUgai Pharmaceutical Co., Gotemba, Japan

Abstract

Background Reports of clinical trials for RA show that the anti-IL-6 receptor antibody tocilizumab (anti-IL-6R) inhibits not only bone erosion but also joint space narrowing [1]. Cartilage destruction is thought to be partly caused by increased expression of enzymes that degrade the cartilage matrix. It has also been reported that oxidative stress is increased in patients with RA [2] and plays a key role in cartilage destruction [3]. However, it is not yet clear how anti-IL-6R inhibits cartilage destruction.

Objectives The purpose of this study was to investigate the effect of anti-IL-6R on cartilage destruction and the levels of the cartilage matrix–degrading enzymes and oxidative stress in a mouse model of collagen-induced arthritis (CIA).

Methods After allocating some mice to a normal group, CIA was triggered in DBA/1J mice by an intradermal injection of bovine type II collagen, and these mice were allocated to a control group or a treated group. Mice in the treated group were injected intraperitoneally with anti-mouse IL-6 receptor antibody (MR16-1). Samples of serum and hind limbs were taken at the peak of swelling (Day 36). The levels of cartilage matrix–degrading enzymes (MMP-3, MMP-13, ADAMTS4, and ADAMTS5) in serum were measured by ELISA. The level of oxidative stress – as indicated by derivatives of reactive oxygen metabolites (d-ROMs) in serum – was measured using a free radical analytical system. The length of the joint space in the hind limbs was analysed by micro-computed tomography.

Results In the control group, MMP-3, MMP-13, ADAMTS5, and d-ROM were significantly higher than in the normal group. ADAMTS4 could not be detected in any mouse. The space between joints in the hind limbs was significantly narrower in the control group than in the normal group, and thicker in the MR16-1 group than in the control group (Figure 1 arrows). The arthritis score and the levels of MMP-3, MMP-13, ADAMTS5, and d-ROM were lower in the MR16-1 group than in the control group.

Conclusions We demonstrated that CIA-induced joint space narrowing was accompanied by increased expression of cartilage matrix–degrading enzymes and oxidative stress. Furthermore, our results also indicated that IL-6 plays an important role in cartilage destruction. Our findings indicate that anti-IL-6R may suppress cartilage destruction by inhibiting the increased expression of cartilage matrix–degrading enzymes and oxidative stress.

References

  1. Kremer et al. Arthritis Rheum. 2011; 63: 609-621.

  2. Hitchon CA et al. Arthritis Res Ther. 2004; 6: 265-278.

  3. Reed KN et al. Mol Cell Biochem. 2014; 397: 195-201.

Disclosure of Interest None declared

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