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… Expand
Effect of genetic polymorphisms in the folate pathway on methotrexate therapy in rheumatic diseases.
TLDR
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. Expand
Sulfasalazine is a potent inhibitor of the reduced folate carrier: implications for combination therapies with methotrexate in rheumatoid arthritis.
TLDR
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. Expand
The use of low dose methotrexate in rheumatoid arthritis - are we entering a new era of therapeutic drug monitoring and pharmacogenomics?
TLDR
There is preliminary evidence that a "pharmacogenetic index" that takes into account the effects of multiple genetic variants maybe useful and both therapeutic drug monitoring using MTXPG concentrations and pharmacogenomics of MTX may prove useful in the future. Expand
Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis.
TLDR
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). Expand
Folates and antifolates in rheumatoid arthritis
Abstract Almost all current standard treatment of care for patients with chronic inflammatory diseases such as rheumatoid arthritis (RA) includes the folate antagonist methotrexate (MTX). Despite theExpand
Auxiliary in vitro and in vivo biological evaluation of hydrogen peroxide sensitive prodrugs of methotrexate and aminopterin for the treatment of rheumatoid arthritis.
TLDR
It is found that prodrug 1, an arylboronic acid ROS-sensitive MTX-prodrug, displays similar in vivo efficacy as MTX at an equimolar dose, while avoiding adverse effects known to restrict MTX treatment. Expand
Methotrexate analogues display enhanced inhibition of TNF-α production in whole blood from RA patients
TLDR
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. Expand
Methotrexate in rheumatoid arthritis.
TLDR
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. Expand
Methotrexate normalizes up-regulated folate pathway genes in rheumatoid arthritis.
TLDR
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. Expand
Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis.
TLDR
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. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 120 REFERENCES
[Effects of methotrexate on leukotriene and derivated lipoxygenase synthesis in polynuclear neutrophils in rheumatoid polyarthritis].
TLDR
It is suggested that MTX in a single dose is responsible for a decrease in the synthesis of LTB4 and 5-LO products in neutrophils and other blood cells in RA patients but does not affect 12-LO activity. Expand
Antifolates in rheumatoid arthritis: a hypothetical mechanism of action.
TLDR
It is hypothesize that blockage of aminoimidazole carboxamide ribotide transformylase, the folate dependent enzyme responsible for the insertion of carbon 2 into the purine ring, produces an immunosuppression mediated by secondary inhibition of adenosine deaminase, and S-adenosyl homocystein hydrolase by aminoimdazolecarboxamide metabolites. Expand
Methotrexate and cyclooxygenase metabolism in cultured human rheumatoid synoviocytes.
TLDR
MTX has an inhibitory effect on IL-1beta stimulated production of PGE2 by cultured human rheumatoid synoviocytes, without affecting either COX mRNA expression. Expand
Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells.
TLDR
The data demonstrate that MTX can selectively delete activated peripheral blood T cells by a CD95-independent pathway, and this property could be used as a new pharmacological end point to optimize dosage and timing of MTX administration. Expand
Effect of methotrexate on blood purine and pyrimidine levels in patients with rheumatoid arthritis.
TLDR
MTX decreases circulating purine and pyrimidine concentrations, and their availability for DNA and RNA synthesis, which may affect immune cell proliferation and protein (cytokine) expression, although localized adenosine concentration changes cannot be excluded. Expand
Methotrexate: its use in the rheumatic diseases.
TLDR
Prospective double blind controlled studies on psoriatic arthritis and rheumatoid arthritis should help establish this drug as the immunosuppressive of choice in these diseases. Expand
The effects of low-dose methotrexate on thymidylate synthetase activity in human peripheral blood mononuclear cells.
TLDR
Low-dose MTX significantly inhibited thymidylate synthetase activity and the proliferation of stimulated PBMC independent of the mode of activation and the concentration of TS mRNA in normal PBMC was upregulated by the presence of MTX. Expand
Supplementation with Folic Acid during Methotrexate Therapy for Rheumatoid Arthritis: A Double-Blind, Placebo-Controlled Trial
TLDR
A larger and longer study to evaluate different doses of folic acid, assuming that toxicity could be reduced without changing the efficacy of methotrexate, and the influence of the folic Acid dose on metotrexate toxicity and efficacy remains controversial. Expand
Reversal of the antiinflammatory effects of methotrexate by the nonselective adenosine receptor antagonists theophylline and caffeine: evidence that the antiinflammatory effects of methotrexate are mediated via multiple adenosine receptors in rat adjuvant arthritis.
TLDR
There is strong evidence that adenosine mediates the antiinflammatory effects of MTX in this model of RA, and the findings suggest that abstinence from caffeine, a ubiquitous food additive and medication, may enhance the therapeutic effects ofMTX in RA. Expand
Methotrexate as a preferential cyclooxygenase 2 inhibitor in whole blood of patients with rheumatoid arthritis.
TLDR
The results clearly show that the anti-inflammatory action of low-dose MTX is partly mediated by a serum factor induced by MTX or a MTX metabolite that preferentially inhibits the activity of COX-2. Expand
...
1
2
3
4
5
...