Evidence map›Paper›PMID 16308339›Full record

ArticleAnnals of the rheumatic diseases2006

Methotrexate modulates the kinetics of adenosine in humans in vivo.

N P Riksen, P Barrera, P H H van den Broek, P L C M van Riel, P Smits, G A Rongen

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In one paragraph

Article in Annals of the rheumatic diseases, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.

  1. Pooled it
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  6. Review
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  10. CD73RMD open · 2025
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  12. Impact of Estrogen on Purinergic Signaling in Microvascular Disease.International journal of molecular sciences · 2025
    Review
  13. Article
  14. The Role of Adenosine in Overcoming Resistance in Sarcomas.International journal of molecular sciences · 2024
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Comorbidities of sarcoidosis.Annals of medicine · 2022
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

N P RiksenDepartment of Pharmacology-Toxicology 149, Radboud University Nijmegen Medical Centre, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands. N.Riksen@aig.umcn.nl
P Barrera
P H H van den Broek
P L C M van Riel
P Smits
G A Rongen
Radboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAnimal studies suggest that the anti-inflammatory effect of methotrexate (MTX) is mediated by increased adenosine concentrations.

objectiveTo assess the effect of MTX on the vasodilator effects of adenosine and the nucleoside uptake inhibitor, dipyridamole, in humans in vivo as a marker for changes in adenosine kinetics.

methodsTen patients with active arthritis were treated with MTX (15 mg/week). Measurements were performed before and after 12 weeks of treatment. At these time points, the activity of adenosine deaminase was measured in isolated lymphocytes, and forearm blood flow (FBF) was determined by venous occlusion plethysmography during administration of adenosine and dipyridamole into the brachial artery.

resultsThe Vmax of adenosine deaminase in lymphocytes was reduced by MTX treatment (p<0.05). MTX significantly enhanced vasodilator response to adenosine (0.5 and 1.5 microg/min/dl of forearm tissue; mean (SE) FBF ratio increased from 1.2 (0.2) to 1.4 (0.2) and 2.2 (0.2) ml/dl/min, respectively, before and from 1.3 (0.1) to 1.8 (0.2) and 3.2 (0.5) ml/dl/min during MTX treatment; p<0.05). Also, dipyridamole-induced vasodilatation (30 and 100 microg/min/dl) was enhanced by MTX (FBF ratio increased from 1.2 (0.2) to 1.5 (0.3) and 1.8 (0.2), respectively, before and from 1.3 (0.1) to 1.8 (0.2) and 2.4 (0.4) during MTX treatment; p<0.05).

conclusionsMTX treatment inhibits deamination of adenosine and potentiates adenosine-induced vasodilatation. Also dipyridamole-induced vasodilatation is enhanced by MTX treatment, suggesting an increased extracellular formation of adenosine. These effects on the adenosine kinetics in humans may contribute to the therapeutic efficacy of MTX.

Indexed as

AdenosineAdenosine DeaminaseAdenosine Deaminase InhibitorsAdultAgedAntirheumatic AgentsArthritis, RheumatoidDipyridamoleDose-Response Relationship, DrugDrug SynergismFemaleForearmHemodynamicsHumansMaleMethotrexateAdenosineAdenosine DeaminaseAdenosine Deaminase InhibitorsAntirheumatic AgentsDipyridamoleMethotrexateVasodilator Agents

Identifiers

PMID16308339
PMCPMC1798086
OpenAlexW2169627285

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.