Improvement of spontaneous locomotor activity with JAK inhibition by JTE-052 in rat adjuvant-induced arthritis

BMC Musculoskeletal Disorders

Mutsuyoshi Matsushita¹  Takayuki Yamaguchi¹  Akira Matsuo¹  Wataru Amano¹  Yukari Kimoto¹  Keisuke Nozawa¹  Yuichi Shinozaki¹  Atsuo Tanimoto¹ 

[1] Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki 569-1125, Osaka, Japan

关键词: Adjuvant-induced arthritis;    Quality of life;    Motor function;    Pain-related behavior;    Spontaneous locomotor activity;    Rheumatoid arthritis;    JTE-052;    JAK inhibition;   

Others  :  1234036
DOI  :  10.1186/s12891-015-0802-0

 received in 2015-03-05, accepted in 2015-11-03,  发布年份 2015

【 摘 要 】

Background

Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to joint destruction, disability, and decreased quality of life (QOL). Inhibition of Janus kinase (JAK) signaling ameliorates articular inflammation and joint destruction in animal models of RA, but its effects on behaviors indicating well-being are poorly understood. In this study, we evaluated the effect of JAK inhibition on spontaneous locomotor activity in rats with adjuvant-induced arthritis, a rodent model of RA.

Methods

Arthritis was induced in male Lewis rats by a single subcutaneous injection of Freund’s complete adjuvant. The novel JAK inhibitor JTE-052 was orally administered for 7 days after the onset of arthritis.

Results

Induction of arthritis suppressed the spontaneous locomotor activity of the rats. Administration of JTE-052 completely improved the spontaneous locomotor activity, with partial reductions in articular inflammation and joint destruction. Hyperalgesia and motor functions were also improved, but the efficacy was not complete. However, serum interleukin (IL)-6 levels were completely decreased at 4 h after administration of the first dose of JTE-052.

Conclusions

This study demonstrated that JAK inhibition improved the spontaneous locomotor activity of rats with adjuvant-induced arthritis, in association with amelioration of pain and physical dysfunction as a consequence of suppression of joint inflammation. Moreover, although further studies are needed, there was possible participation of IL-6 downregulation in the improvement of locomotor activity by JAK inhibition.

【 授权许可】

   
2015 Tanimoto et al.

【 图 表 】

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