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SAT0041 Metformin downregulates TH17 differentiation and attenuates murine autoimmune arthritis
  1. K.Y. Kang1,
  2. Y.-K. Kim2,
  3. H. Yi2,
  4. J. Kim2,
  5. H.-R. Jung3,
  6. I.J. Kim4,
  7. J.H. Ju5
  1. 1Division of Rheumatology, Internal Medicine, Chungbuk National University Hospital, Cheongju
  2. 2Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea, seoul, Korea, Republic Of
  3. 3Division of Rheumatology, Internal Medicine, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea
  4. 4Division of Rheumatology, Internal Medicine, Hallym University
  5. 5Division of Rheumatology, Internal Medicine, The Catholic University of Korea, seoul, Korea, Republic Of


Background Metformin, a pharmacological AMPK activator, is one of the most widely used drugs for diabetes. In recent years, metformin takes a growing interests for its anti-inflammatory property.

Objectives This study was undertaken to evaluate anti-inflammatory effect of metformin in collagen antibody-induced arthritis (CAIA) in mice. The effect of metformin on the differentiation of Th17 was also investigated in vivo and vitro.

Methods CAIA mice in which inflammatory arthritis was developing were treated with metformin. Metformin was treated 100mg/kg i.p. in low dose group and 150mg/kg i.p in high dose group. The effect of treatment on clinical disease activity and histological joint destruction were studied. The propotion of Th17 in axillary draining lymph node (DLN) from CAIA mice and metformin-treated mice was analysed by FACS. Naïve T cells from CAIA mice and metformin-treated mice were differentiated to Th17 on ex vivo stimulation. The effect of metformin on Th17 differentaion in vitro was also investigated in naive T cells from DBA/1 mice.

Results Metformin attenuated arthritis scores and bone destruction in CAIA mice. Metformin also decreased serum levels of inflammatory cytokines such as IL-17, TNF-a and IL-6. The number of Th17 in axillary DLN was significantly reduced in metformin treated group compared with the control group. Naive T cells of metformin treated group, as compared with those of controls, less differentiated into Th17 on ex vivo stimulation. The stimulation of CD4(+) T cells with metformin in vitro decreased Th17 differentiation in a dose-dependent manner. The transcriptional factors of Th17, such as STAT3 and RORγt, were down-regulated by metformin through AMPK-mTOR pathway.

Conclusions These findings indicated that anti-inflammatory effect of metformin was due to inhibit differentiation of Th17 via AMPK-mTOR pathway. It suggests that metformin may have a possible therapeutic value for the treatment of rheumatoid arthritis.

Disclosure of Interest None Declared

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