Evidence map›Paper›PMID 29429002›Full record

ArticleTranslational stroke research2018

Interleukin 6-Mediated Endothelial Barrier Disturbances Can Be Attenuated by Blockade of the IL6 Receptor Expressed in Brain Microvascular Endothelial Cells.

Kinga G Blecharz-Lang, Josephin Wagner, Alexa Fries, Melina Nieminen-Kelhä, Jörg Rösner, Ulf C Schneider, Peter Vajkoczy

Abstract read
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In one paragraph

Article in Translational stroke research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 2 pooled it
7.2field-weighted citation impact, top 2% 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

87 citing papers in PubMed, 2 syntheses or guidelines pooled it, 123 citations in OpenAlex.

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  17. Role of astrocytes connexins - pannexins in acute brain injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  18. Frontiers in cellular and infection microbiology · 2025
    Article
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27 more citing papers are in PubMed but not listed here.

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

7 authors at 3 institutions in 1 country.

Kinga G Blecharz-LangCharité-Universitätsmedizin Berlin, corporate of Freie Universität Berlin, Department of Experimental Neurosurgery, Humbold-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
Josephin WagnerCharité-Universitätsmedizin Berlin, corporate of Freie Universität Berlin, Department of Experimental Neurosurgery, Humbold-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
Alexa FriesCharité-Universitätsmedizin Berlin, corporate of Freie Universität Berlin, Department of Experimental Neurosurgery, Humbold-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
Melina Nieminen-KelhäCharité-Universitätsmedizin Berlin, corporate of Freie Universität Berlin, Department of Experimental Neurosurgery, Humbold-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
Jörg RösnerNeuroscience Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117, Berlin, Germany.
Ulf C SchneiderCharité-Universitätsmedizin Berlin, corporate of Freie Universität Berlin, Department of Experimental Neurosurgery, Humbold-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
Peter VajkoczyCharité-Universitätsmedizin Berlin, corporate of Freie Universität Berlin, Department of Experimental Neurosurgery, Humbold-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany. peter.vajkoczy@charite.de.
Humboldt-Universität zu Berlin · DEBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DEFreie Universität Berlin · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Compromised blood-brain barrier (BBB) by dysregulation of cellular junctions is a hallmark of many cerebrovascular disorders due to the pro-inflammatory cytokines action. Interleukin 6 (IL6) is implicated in inflammatory processes and in secondary brain injury after subarachnoid hemorrhage (SAH) but its role in the maintenance of cerebral endothelium still requires a precise elucidation. Although IL6 has been shown to exert pro-inflammatory action on brain microvascular endothelial cells (ECs), the expression of one of the IL6 receptors, the IL6R is controversially discussed. In attempt to reach more clarity in this issue, we present here an evident baseline expression of the IL6R in BBB endothelium in vivo and in an in vitro model of the BBB, the cEND cell line. A significantly increased expression of IL6R and its ligand was observed in BBB capillaries 2 days after experimental SAH in mice. In vitro, we saw IL6 administration resulting in an intracellular and extracellular elevation of IL6 protein, which was accompanied by a reduced expression of tight and adherens junctions, claudin-5, occludin, and vascular-endothelial (VE-) cadherin. By functional assays, we could demonstrate IL6-incubated brain ECs to lose their endothelial integrity that can be attenuated by inhibiting the IL6R. Blockade of the IL6R by a neutralizing antibody has reconstituted the intercellular junction expression to the control level and caused a restoration of the transendothelial electrical resistance of the cEND cell monolayer. Our findings add depth to the current understanding of the involvement of the endothelial IL6R in the loss of EC integrity implicating potential therapy options.

Indexed as

AnimalsAntibodiesAntigens, CDBlood-Brain BarrierCadherin 5CadherinsCell Line, TransformedCell ProliferationCytokinesDisease Models, AnimalElectric ImpedanceEndothelial CellsEndothelium, VascularGene Expression RegulationInterleukin-6Magnetic Resonance ImagingAntibodiesAntigens, CDCadherin 5CadherinsCytokinesInterleukin-6OccludinReceptors, Interleukin-6Blood-brain barrierCytokineEndothelial cellsInflammationInterleukin 6Subarachnoid hemorrhage

Identifiers

PMID29429002
OpenAlexW2790000742

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.