Evidence map›Paper›PMID 21211004›Full record

Trial reportCritical care (London, England)2011

Circulating adenosine increases during human experimental endotoxemia but blockade of its receptor does not influence the immune response and subsequent organ injury.

Bart P Ramakers, Niels P Riksen, Petra van den Broek, Barbara Franke, Wilbert H M Peters, Johannes G van der Hoeven, Paul Smits, Peter Pickkers

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Critical care (London, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00513110 (A Possible Therapeutic Role for Adenosine During Inflammation), which is not on this map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.9field-weighted citation impact, top 16% 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.

NCT00513110 phase1completednot on this map

A Possible Therapeutic Role for Adenosine During Inflammation

TypeinterventionalSponsorRadboud University Medical CenterRan2007 to 2008Enrolled33ConditionsEndotoxemiaArmsAMPD1 polymorphism, Caffeine infusion, placebo
3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 39 citations in OpenAlex.

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  16. Adenosine kinase determines the degree of brain injury after ischemic stroke in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2011
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Bart P RamakersDepartment of Intensive Care Medicine, Radboud University Nijmegen Medical Center, Geert Grooteplein 10, 6500 HB Nijmegen, The Netherlands. p.pickkers@ic.umcn.nl
Niels P Riksen
Petra van den Broek
Barbara Franke
Wilbert H M Peters
Johannes G van der Hoeven
Paul Smits
Peter Pickkers
Radboud University Nijmegen · NLRadboud University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionPreclinical studies have shown that the endogenous nucleoside adenosine prevents excessive tissue injury during systemic inflammation. We aimed to study whether endogenous adenosine also limits tissue injury in a human in vivo model of systemic inflammation. In addition, we studied whether subjects with the common 34C > T nonsense variant (rs17602729) of adenosine monophosphate deaminase (AMPD1), which predicts increased adenosine formation, have less inflammation-induced injury.

methodsIn a randomized double-blinded design, healthy male volunteers received 2 ng/kg E. Coli LPS intravenously with (n = 10) or without (n = 10) pretreatment with the adenosine receptor antagonist caffeine (4 mg/kg body weight). In addition, lipopolysaccharide (LPS) was administered to 10 subjects heterozygous for the AMPD1 34C > T variant.

resultsThe increase in adenosine levels tended to be more pronounced in the subjects heterozygous for the AMPD1 34C > T variant (71 ± 22%, P=0.04), compared to placebo- (59 ± 29%, P=0.012) and caffeine-treated (53 ± 47%, P=0.29) subjects, but this difference between groups did not reach statistical significance. Also the LPS-induced increase in circulating cytokines was similar in the LPS-placebo, LPS-caffeine and LPS-AMPD1-groups. Endotoxemia resulted in an increase in circulating plasma markers of endothelial activation [intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)], and in subclinical renal injury, measured by increased urinary excretion of tubular injury markers. The LPS-induced increase of these markers did not differ between the three groups.

conclusionsHuman experimental endotoxemia induces an increase in circulating cytokine levels and subclinical endothelial and renal injury. Although the plasma adenosine concentration is elevated during systemic inflammation, co-administration of caffeine or the presence of the 34C > T variant of AMPD1 does not affect the observed subclinical organ damage, suggesting that adenosine does not affect the inflammatory response and subclinical endothelial and renal injury during human experimental endotoxemia.

trial registrationClinicalTrials (NCT): NCT00513110.

Indexed as

AdenosineAMP DeaminaseCaffeineDouble-Blind MethodEndotoxemiaEscherichia coliHumansImmunity, InnateInflammationKidneyLipopolysaccharidesMalePurinergic P1 Receptor AntagonistsReceptors, Purinergic P1AdenosineAMPD1 protein, humanAMP DeaminaseCaffeineLipopolysaccharidesPurinergic P1 Receptor AntagonistsReceptors, Purinergic P1

Identifiers

PMID21211004
PMCPMC3222030
OpenAlexW2167158961

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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.