PT  - JOURNAL ARTICLE
AU  - Bruce N. Cronstein
TI  - Low-Dose Methotrexate: A Mainstay in the Treatment of Rheumatoid Arthritis
AID  - 10.1124/pr.57.2.3
DP  - 2005 Jun 01
TA  - Pharmacological Reviews
PG  - 163--172
VI  - 57
IP  - 2
4099  - http://pharmrev.aspetjournals.org/content/57/2/163.short
4100  - http://pharmrev.aspetjournals.org/content/57/2/163.full
SO  - Pharmacol Rev2005 Jun 01; 57
AB  - 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.