Evidence map›Paper›PMID 26661249›Full record

ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2016

Recombinant human interleukin-1 receptor antagonist promotes M1 microglia biased cytokines and chemokines following human traumatic brain injury.

Adel Helmy, Mathew R Guilfoyle, Keri L H Carpenter, John D Pickard, David K Menon, Peter J Hutchinson

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 2 pooled it
5.2field-weighted citation impact, top 5% 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

54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 85 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
  5. Observational
  6. Review
  7. Revisiting the critical roles of reactive microglia in traumatic brain injury.International journal of surgery (London, England) · 2025
    Review
  8. Article
  9. Review
  10. Review
  11. Interleukin-1 Receptor Antagonist as Therapy for Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Tackling Neuroinflammation After Traumatic Brain Injury: Complement Inhibition as a Therapy for Secondary Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Review
  17. Review
  18. Review
  19. Review
  20. Article
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

6 authors at 1 institution in 1 country.

Adel HelmyDivision of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK adelhelmy@cantab.net.
Mathew R GuilfoyleDivision of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Keri L H CarpenterDivision of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
John D PickardDivision of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
David K MenonWolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Peter J HutchinsonDivision of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
University of Cambridge · GB

Funding

Department of Health NIHR-RP-R3-12-013Medical Research Council G0001354Medical Research Council G0600986Medical Research Council G0601025Medical Research Council G0802251Medical Research Council G1000183Medical Research Council G1002277Medical Research Council G9439390
6 · The paper itself

Abstract

Interleukin-1 receptor antagonist (IL1ra) has demonstrated efficacy in a wide range of animal models of neuronal injury. We have previously published a randomised controlled study of IL1ra in human severe TBI, with concomitant microdialysis and plasma sampling of 42 cytokines and chemokines. In this study, we have used partial least squares discriminant analysis to model the effects of drug administration and time following injury on the cytokine milieu within the injured brain. We demonstrate that treatment with rhIL1ra causes a brain-specific modification of the cytokine and chemokine response to injury, particularly in samples from the first 48 h following injury. The magnitude of this response is dependent on the concentration of IL1ra achieved in the brain extracellular space. Chemokines related to recruitment of macrophages from the plasma compartment (MCP-1) and biasing towards a M1 microglial phenotype (GM-CSF, IL1) are increased in patient samples in the rhIL1ra-treated patients. In control patients, cytokines and chemokines biased to a M2 microglia phenotype (IL4, IL10, MDC) are relatively increased. This pattern of response suggests that a simple classification of IL1ra as an 'anti-inflammatory' cytokine may not be appropriate and highlights the importance of the microglial response to injury.

Indexed as

AdolescentAdultBrainBrain Injuries, TraumaticChemokinesCytokinesFemaleHumansInterleukin 1 Receptor Antagonist ProteinLeast-Squares AnalysisMaleMicrodialysisMicrogliaMiddle AgedReceptors, Interleukin-1Recombinant ProteinsChemokinesCytokinesInterleukin 1 Receptor Antagonist ProteinReceptors, Interleukin-1Recombinant Proteinsbrain traumaChemokinesinflammationmicroglianeurochemistry

Identifiers

PMID26661249
PMCPMC4976751
OpenAlexW2417746379

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.