Evidence map›Paper›PMID 26858459›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates.

Thierry Roger, Anina Schneider, Manuela Weier, Fred C G J Sweep, Didier Le Roy, Jürgen Bernhagen, Thierry Calandra, Eric Giannoni

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

47 citing papers in PubMed, 71 citations in OpenAlex.

  1. Trial
  2. CDK4/6 Inhibition Induces CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  17. Distinct Group BInfection and immunity · 2021
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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 3 institutions in 3 countries.

Thierry RogerInfectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;ORCID http://orcid.org/0000-0002-9358-0109
Anina SchneiderInfectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; Service of Neonatology, Department of Pediatrics, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;
Manuela WeierInfectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; Service of Neonatology, Department of Pediatrics, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;
Fred C G J SweepDepartment of Laboratory Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands;
Didier Le RoyInfectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;
Jürgen BernhagenInstitute of Biochemistry and Molecular Cell Biology, Rheinisch-Westfälisch Technische Hochschule Aachen University, D-52074 Aachen, Germany; Vascular Biology, Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, D-81377 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), D-81377 Munich, Germany.
Thierry CalandraInfectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland;
Eric GiannoniInfectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; Service of Neonatology, Department of Pediatrics, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland; Eric.Giannoni@chuv.ch.
University of Lausanne · CHMunich Cluster for Systems Neurology · DERadboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis.

Indexed as

AdultAnimalsEscherichia coliExtracellular Signal-Regulated MAP KinasesFemaleGene Expression RegulationHumansImmunity, InnateInfant, NewbornIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMAP Kinase Signaling SystemMiceMonocytesStreptococcus agalactiaeExtracellular Signal-Regulated MAP KinasesIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMIF protein, humanMif protein, mouseadenosineEscherischia colinewbornsprostaglandinsepsis

Identifiers

PMID26858459
PMCPMC4776487
OpenAlexW2261342640

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.