%0 Journal Article %A Bruce N. Cronstein %T Low-Dose Methotrexate: A Mainstay in the Treatment of Rheumatoid Arthritis %D 2005 %R 10.1124/pr.57.2.3 %J Pharmacological Reviews %P 163-172 %V 57 %N 2 %X Methotrexate administered weekly in low doses is a mainstay in the therapy of rheumatoid arthritis. Although originally developed as a folate antagonist for the treatment of cancer, its mechanism of action in the therapy of rheumatoid arthritis remains less clear. Several mechanisms have been proposed including inhibition of T cell proliferation via its effects on purine and pyrimidine metabolism, inhibition of transmethylation reactions required for the prevention of T cell cytotoxicity, interference with glutathione metabolism leading to alterations in recruitment of monocytes and other cells to the inflamed joint, and promotion of the release of the endogenous anti-inflammatory mediator adenosine. These mechanisms of action and the role of methotrexate in the suppression of rheumatoid arthritis are reviewed. %U https://pharmrev.aspetjournals.org/content/pharmrev/57/2/163.full.pdf