Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis.
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.
Cronstein
Bruce N
BN
Pathology and Pharmacology, Division of Clinical Pharmacology, Department of Medicine, NYU School of Medicine, 550 First Ave., New York, NY 10016, USA. cronsb01@med.nyu.edu
D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*
D018501:Antirheumatic Agents; D008727:Methotrexate