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

Bruce N Cronstein1

  • 1Pathology 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

Pharmacological Reviews
|May 26, 2005
PubMed

Insights

Low-dose methotrexate is a key rheumatoid arthritis treatment. Its precise anti-inflammatory mechanisms, involving purine/pyrimidine metabolism, T cell function, and adenosine release, are reviewed for disease suppression.

Area of Science:

  • Immunology
  • Pharmacology
  • Rheumatology

Background:

  • Methotrexate (MTX) is a widely used weekly low-dose therapy for rheumatoid arthritis (RA).
  • Originally developed as a cancer treatment (folate antagonist), its mechanism in RA is not fully understood.
  • Several potential pathways are proposed for MTX's therapeutic effects in RA.

Purpose of the Study:

  • To review the proposed mechanisms of action for low-dose methotrexate in rheumatoid arthritis therapy.
  • To elucidate the role of methotrexate in suppressing rheumatoid arthritis.

Main Methods:

  • Review of existing literature on methotrexate's biochemical and cellular effects.
  • Analysis of proposed mechanisms including metabolic inhibition, immune cell modulation, and mediator release.

Main Results:

  • Proposed mechanisms include inhibition of T cell proliferation through purine/pyrimidine metabolism.
  • Interference with transmethylation and glutathione metabolism affects immune cell recruitment.
  • Promotion of endogenous anti-inflammatory adenosine release is another key pathway.

Conclusions:

  • Multiple complex mechanisms contribute to methotrexate's efficacy in rheumatoid arthritis.
  • Understanding these pathways is crucial for optimizing RA treatment strategies.

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