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Obesity does not diminish the efficacy of IL-6 signalling blockade in mice with collagen-induced arthritis

1, 2, 3, 4, 5

  1. Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
  2. Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
  3. Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
  4. Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan. yogoknj@chugai-pharm.co.jp
  5. Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.

CER9872 Submission on line
2017 Vol.35, N°6 - PI 0893, PF 0898
Full Papers

Rheumatology Article

 

Abstract

OBJECTIVES:
Obese rheumatoid arthritis patients often have higher disease activity and a poorer response to treatment than do non-obese patients. The present study aims to clarify the influence of obesity on the action of IL-6 and to evaluate the efficacy of IL-6 signalling blockade in arthritis with obesity.
METHODS:
Mice were fed a high-fat diet for 5 weeks, and the influence of this diet on macrophages and type II collagen-induced arthritis was investigated.
RESULTS:
The mice fed the high-fat diet showed greater expression of macrophage marker F4/80, not only in subcutaneous fat but also in knee synovium and the calcaneal region, than did the mice fed a normal diet. Furthermore, macrophages isolated from mice on the high-fat diet tended to show higher expression of cyclooxygenase-2 following IL-6 stimulation than did macrophages from mice fed the normal diet. Moreover, mice fed the normal or high-fat diet were immunised with type II collagen, and were treated with anti-mouse IL-6 receptor antibody (MR16-1). The anti-arthritis effect of MR16-1 was not reduced in mice fed the high-fat diet compared to mice fed the normal diet (inhibition ratio: 87% vs. 62%). Furthermore, at the peak of arthritis, cyclooxygenase-2 expression in the calcaneal region of mice fed the high-fat diet was higher than that in the mice fed the normal diet.
CONCLUSIONS:
These results suggested that a high-fat diet induces inflammatory changes in the synovium. We demonstrated that IL-6 signalling blockade by an anti-IL-6 receptor antibody can be effective in treating arthritis, even with obesity.

PMID: 28421996 [PubMed]

Received: 26/08/2016 - Accepted : 14/02/2017 - In Press: 18/04/2017 - Published: 11/12/2017