Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis

@article{Cutolo2001AntiinflammatoryMO,
  title={Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis},
  author={Maurizio Cutolo and Alberto Sulli and Carmen Pizzorni and Bruno Seriolo and Rainer H. Straub},
  journal={Annals of the Rheumatic Diseases},
  year={2001},
  volume={60},
  pages={729 - 735}
}
Methotrexate (MTX) is a folate analogue originally synthesised in the 1940s and designed to inhibit dihydrofolate reductase.1 Reduced folate (tetrahydrofolate) is the proximal single carbon donor in several reactions involved in the de novo synthetic pathways for purine and pyrimidine precursors of DNA and RNA required for cell proliferation. Furthermore, tetrahydrofolate plays a part in a second important biochemical step: the methionine-homocysteine cycle, which is necessary to provide a… 

Effect of genetic polymorphisms in the folate pathway on methotrexate therapy in rheumatic diseases.

Prospective studies, standardizing the definitions of response and toxicity, and application of genome-wide approaches may advance the search for genetic predictors of MTX response.

Sulfasalazine is a potent inhibitor of the reduced folate carrier: implications for combination therapies with methotrexate in rheumatoid arthritis.

Interactions of sulfasalazine with reduced folate carrier (RFC) provide a biochemical rationale for the onset of (sub)clinical folate deficiency during SSZ treatment, and the lack of additivity/synergism of the combination of SSZ and MTX when these disease-modifying antirheumatic drugs are administered simultaneously.

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

Recent data supporting the methotrexate mechanisms of action are presented, which are likely to account for its anti-proliferative and immunosuppressive effects in rheumatoid arthritis (RA).

Folates and antifolates in rheumatoid arthritis

An overview will be presented of strategies that may assist in the future design of rationalized and personalized targeted therapies with a folate antagonist.

Methotrexate analogues display enhanced inhibition of TNF-α production in whole blood from RA patients

New-generation antifolates PT523, PT644, raltitrexed, and GW1843 proved to be potent inhibitors of TNF-α production in activated T cells from all three groups of RA patients and from healthy volunteers.

Methotrexate in rheumatoid arthritis.

Methotrexate, an analogue of folic acid and of aminopterin, is the most commonly used DMARD and is now prescribed worldwide to at least 500,000 patients with RA and has one of the best efficacy/toxicity ratios.

Methotrexate normalizes up-regulated folate pathway genes in rheumatoid arthritis.

These results suggest that under inflammatory conditions, basal folate metabolism in the peripheral blood cells of RA patients is markedly up-regulated, and treatment with MTX restores folates metabolism to normal levels.

Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis.

It is shown that there is no impact of effective MTX dose represented by EMTX on blood adenosine concentration in JIA patients and it is likely that local release ofadenosine at inflamed tissues is responsible for its action which may not be reflected by sustained increase of its blood concentration.
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References

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