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Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis Cronstein BNPharmacol Rev 2005[Jun]; 57 (2): 163-72Methotrexate 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.|Animals[MESH]|Antirheumatic Agents/administration & dosage/*therapeutic use[MESH]|Arthritis, Rheumatoid/*drug therapy/genetics/immunology/metabolism[MESH]|Dose-Response Relationship, Drug[MESH]|Humans[MESH]|Methotrexate/administration & dosage/*therapeutic use[MESH] |
