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Rheumatology Advance Access published online on November 28, 2007
Rheumatology, doi:10.1093/rheumatology/kem279
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Review

Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis

J. A. M. Wessels1, T. W. J. Huizinga2 and H.-J. Guchelaar1

1Department of Clinical Pharmacy and Toxicology and 2Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands

Correspondence to: H.-J. Guchelaar, Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: H.J.Guchelaar{at}lumc.nl


  Abstract

This review presents recent data supporting the methotrexate (MTX) mechanisms of action, which are likely to account for its anti-proliferative and immunosuppressive effects in rheumatoid arthritis (RA). The effects of MTX in vivo may be mediated by reducing cell proliferation, increasing the rate of apoptosis of T cells, increasing endogenous adenosine release, altering the expression of cellular adhesion molecules, influencing production of cytokines, humoral responses and bone formation. Several reports indicate that the effects of MTX are influenced by genetic variants, specific dynamic processes and micro-environmental elements such as nucleotide deprivation or glutathione levels. The challenge for the future will be linking biological and genetic markers relevant to the response to MTX in RA.

KEY WORDS: Methotrexate, Molecular mechanisms of action, Pharmacology, Rheumatoid arthritis

Submitted 5 February 2007; revised version accepted 10 September 2007.
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