Effectiveness of methotrexate in combination therapy in a rat collagen-induced arthritis model

This study was to investigate the effect of methotrexate in combination therapy by the characteristic cytokine in Th17 cells and the frequency of Tregs, which involved in the induction and pathological progress of rheumatoid arthritis (RA). The collagen-induced arthritis rats were treated with methotrexate + prednisone, methotrexate + disease-modifying rheumatic drugs (DMARDs) and methotrexate + TNFi, respectively. The following parameters were observed to evaluate three treatments: the frequency and function of Th17 cells and Tregs, the scores of X-rays, H&E staining and immunohistochemistry. For rats starting methotrexate + prednisone (low doses), the frequency and suppressive function of Th17 cells decreased while the frequency of Tregs increased, which were the same in methotrexate + TNFi. Immunohistochemical in the pathological sections of ankle joint showed the same results. The effect of methotrexate + DMARDs treatment was slightly inferior to the other combination therapies. In summary, rats treated with methotrexate + prednisone can achieve high level of Tregs and low level of Th17 cells and IL-17. Low doses of glucocorticoid suggesting a critical role in the pathogenesis of rheumatoid arthritis may have the similar effect as DMARDs.