Dimethyl Fumarate Ameliorates Collagen-Induced Arthritis in Lewis Rats by Modulation of Th17/Treg Balance

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects approximately 1% of the world's population. Due to its anti-inflammatory effects, Dimethyl fumarate (DMF) can be used to treat RA. However, its molecular mechanisms have not yet been fully elucidated. In this study, an animal model of collagen-induced arthritis (CIA) was used to investigate DMF's In Vivo effects and probable mechanism of action on arthritis. Twenty-five rats were divided into five groups: healthy control group (normal), CIA rats without any treatment (CIA control), CIA rats treated with vehicle, CIA rats treated with methotrexate (MTX), and CIA rats treated with DMF. Hind paw swelling and arthritis score were measured to evaluate DMF effects on the disease progression. Rats were killed on day 28; the plasma levels of IL-17, IL-10, and anti-collagen type II (CII) were measured by the ELISA method, and the percentage of Th17 and Treg cells in different groups was determined by flow cytometry. DMF significantly reduced the arthritis score, hind paw swelling, cartilage destruction, and joint inflammation in CIA rats. The level of CII and IL-17 was also lower in the DMF-treated group compared to the untreated group. The level of IL-10 was higher in the DMF-treated rats. Furthermore, the percentage of Th17 was lower, and the percentage of Treg was higher in DMF-treated rats compared to the control group. DMF demonstrated anti-arthritic activity by reducing the arthritis score, hind paw swelling, cartilage destruction, joint inflammation, and modulation of Treg/Th17 cells. Therefore, DMF may be considered as a new therapeutic agent in RA.