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Pharmacol Rev. 2005 Jun;57(2):163-72.

Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis.

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Pathology and Pharmacology, Division of Clinical Pharmacology, Department of Medicine, NYU School of Medicine, 550 First Ave., New York, NY 10016, USA.


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.

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