Trial reportEBioMedicine2018
Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation.
Open access · goldAbstract readClinical Trial
In one paragraph
Trial report in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 2 pooled it
5.5field-weighted citation impact, top 4% of its field
What it found
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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.
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.
Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- Pooled it
- Effects of Intermittent Normobaric Hypoxia on Health-Related Outcomes in Healthy Older Adults: A Systematic Review.Sports medicine - open · 2023Pooled it
- The immunomodulatory effect of sugammadex in vitro and after total hip arthroplasty : A randomised controlled pilot and retrospective cohort study.European journal of anaesthesiology · 2025Trial
- Brain-Derived neurotrophic factor and inflammatory biomarkers are unaffected by acute and chronic intermittent hypoxic-hyperoxic exposure in geriatric patients: a randomized controlled trial.Annals of medicine · 2024Trial
- Remote ischaemic preconditioning does not modulate the systemic inflammatory response or renal tubular stress biomarkers after endotoxaemia in healthy human volunteers: a single-centre, mechanistic, randomised controlled trial.British journal of anaesthesia · 2019Trial
- Enhancing Exercise Performance Under Hypoxia: A Network Meta-Analysis and Animal Experimental Validation of Plant Bioactive Compounds.Nutrients · 2026Article
- Effects of a 6-Week Intermittent Hypoxia-Hyperoxia Exposure Program on Blood Pressure, Respiratory Function, Cardiac Autonomic Nervous Activity and CRP Levels in Older Adults: A Randomized Clinical Trial.Sports (Basel, Switzerland) · 2026Article
- The immunology of sepsis: translating new insights into clinical practice.Nature reviews. Nephrology · 2026Review
- Effects of administration of a non-specific immunostimulant prior to mating on pregnancy establishment and fetal and placental development in mice.Biochemistry and biophysics reports · 2025Article
- Hypoxia Supports LPS-Driven Tolerance and Functional Activation in BV-2 Microglial Cells.Biology · 2025Article
- Can hypoxic exercise retard cellular senescence? A narrative review.European review of aging and physical activity : official journal of the European Group for Research into Elderly and Physical Activity · 2024Review
- The chronic leukocyte and inflammatory cytokine responses of older adults to resistance training in normobaric hypoxia; a randomized controlled trial.BMC sports science, medicine & rehabilitation · 2024Article
- Neo-epitope detection identifies extracellular matrix turnover in systemic inflammation and sepsis: an exploratory study.Critical care (London, England) · 2024Article
- Effects of Hypoxia on Cerebral Microvascular Angiogenesis: Benefits or Damages?Aging and disease · 2023Review
- Identification of key pathways, genes and immune cell infiltration in hypoxia of high-altitude acclimatizationFrontiers in genetics · 2023Article
- The Hypoxia-Adenosine Link during Myocardial Ischemia-Reperfusion Injury.Biomedicines · 2022Review
- Intermittent Hypoxia as a Therapeutic Tool to Improve Health Parameters in Older Adults.International journal of environmental research and public health · 2022Article
- Sevoflurane Dampens Acute Pulmonary Inflammation via the Adenosine Receptor A2B and Heme Oxygenase-1.Cells · 2022Article
- Reprogramming of glucocorticoid receptor function by hypoxia.EMBO reports · 2022Article
- Effects of Prolonged Exposure to Hypobaric Hypoxia on Oxidative Stress: Overwintering in Antarctic Concordia Station.Oxidative medicine and cellular longevity · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 3 institutions in 3 countries.
Dorien KiersDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Anesthesiology, Radboud University Medical Centre, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
Ben WielockxHeisenberg Research Group, Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany.
Esther PetersDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, the Netherlands.
Lucas T van EijkDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
Jelle GerretsenDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
Aaron JohnDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
Emmy JanssenDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
Rianne GroeneveldDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
Mara PetersDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
Lars DamenDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
Ana M MenesesHeisenberg Research Group, Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany.
Anja KrügerHeisenberg Research Group, Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany.
Jeroen D LangereisRadboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center, Nijmegen, the Netherlands.
Aldert L ZomerRadboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center, Nijmegen, the Netherlands; Centre for Molecular and Biomolecular Informatics (CMBI) Bacterial Genomics, Radboud University Medical Center, Nijmegen, the Netherlands.
Michael R BlackburnDepartment of Biochemistry & Molecular Biology, McGovern Medical School, University of Texas, USA.
Leo A JoostenRadboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
Mihai G NeteaRadboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
Niels P RiksenRadboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
Johannes G van der HoevenDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
Gert-Jan SchefferDepartment of Anesthesiology, Radboud University Medical Centre, Nijmegen, the Netherlands.
Holger K EltzschigCenter for Perioperative Medicine, Department of Anesthesiology, McGovern Medical School, The University of Texas Health Science Center, Houston, USA.
Peter PickkersDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
Matthijs KoxDepartment of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: matthijs.kox@radboudumc.nl.
Radboud University Nijmegen · NLTechnische Universität Dresden · DEThe University of Texas Health Science Center at Houston · US
Funding
Trangenic Mouse Breeding CoreP01HL114457 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ZHANG, YUJIN · 2013 to 2017
$10.0MNovel Immunologic Effects of Semaphorin 7a in IPFR01HL109233 · NHLBI · YALE UNIVERSITY · PI HERZOG, ERICA L · 2011 to 2019
$3.7MHypoxia-Inducible Factors in Acetaminophen-Induced Liver Injury.R01DK109574 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ELTZSCHIG, HOLGER K., JU, CYNTHIA · 2016 to 2019
$1.8MProton Pump Inhibitors for Perioperative Acute Kidney InjuryR01DK097075 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ELTZSCHIG, HOLGER K. · 2013 to 2017
$1.7MHypoxia Inducible Factor in Acute Lung InjuryR01HL098294 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ELTZSCHIG, HOLGER K. · 2011 to 2014
$1.6MAmphiregulin Signaling in Perioperative Cardio-ProtectionR01HL119837 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ELTZSCHIG, HOLGER K. · 2014 to 2017
$1.5MMicroRNA Shuttling during Acute Respiratory Distress SyndromeR01HL133900 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ELTZSCHIG, HOLGER K. · 2017 to 2020
$1.5MReduction of kidney progressive fibrosis by A2A adenosine receptor activation: PR01DK082509 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI GARCIA, GABRIELA E · 2011 to 2015
$1.3MNHLBI NIH HHS P01 HL114457NHLBI NIH HHS R01 HL098294NHLBI NIH HHS R01 HL109233NHLBI NIH HHS R01 HL119837NHLBI NIH HHS R01 HL133900NIDDK NIH HHS R01 DK082509NIDDK NIH HHS R01 DK097075NIDDK NIH HHS R01 DK109574
Abstract
Hypoxia and inflammation are closely intertwined phenomena. Critically ill patients often suffer from systemic inflammatory conditions and concurrently experience short-lived hypoxia. We evaluated the effects of short-term hypoxia on systemic inflammation, and show that it potently attenuates pro-inflammatory cytokine responses during murine endotoxemia. These effects are independent of hypoxia-inducible factors (HIFs), but involve augmented adenosine levels, in turn resulting in an adenosine 2B receptor-mediated post-transcriptional increase of interleukin (IL)-10 production. We translated our findings to humans using the experimental endotoxemia model, where short-term hypoxia resulted in enhanced plasma concentrations of adenosine, augmentation of endotoxin-induced circulating IL-10 levels, and concurrent attenuation of the pro-inflammatory cytokine response. Again, HIFs were shown not to be involved. Taken together, we demonstrate that short-term hypoxia dampens the systemic pro-inflammatory cytokine response through enhanced purinergic signaling in mice and men. These effects may contribute to outcome and provide leads for immunomodulatory treatment strategies for critically ill patients.
Indexed as
AdenosineAnimalsDisease Models, AnimalEndotoxemiaHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitInterleukin-10MiceReceptors, Purinergic P1Up-RegulationAdenosineHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitIL10 protein, humanInterleukin-10Receptors, Purinergic P1AdenosineAdenosine 2B receptorCytokinesEndotoxinHypoxia
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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.