Evidence map›Paper›PMID 25896970›Full record

ArticleJournal of neuroinflammation2015

Astrocyte response to IFN-γ limits IL-6-mediated microglia activation and progressive autoimmune encephalomyelitis.

Carine Savarin, David R Hinton, Alice Valentin-Torres, Zhihong Chen, Bruce D Trapp, Cornelia C Bergmann, Stephen A Stohlman

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

59 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.

  1. Pooled it
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  16. Microglia and Brain Disorders: The Role of Vitamin D and Its Receptor.International journal of molecular sciences · 2023
    Review
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  18. Bystander activation of microglia byFrontiers in immunology · 2023
    Article
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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

7 authors at 2 institutions in 1 country.

Carine SavarinDepartment of Neurosciences NC-30, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. savaric@ccf.org.
David R HintonDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. dhinton@usc.edu.
Alice Valentin-TorresDepartment of Neurosciences NC-30, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. valenta@ccf.org.
Zhihong ChenDepartment of Neurosciences NC-30, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. chenz2@ccf.org.
Bruce D TrappDepartment of Neurosciences NC-30, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. trappb@ccf.org.
Cornelia C BergmannDepartment of Neurosciences NC-30, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. bergmac@ccf.org.
Stephen A StohlmanDepartment of Neurosciences NC-30, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. stohlms2@ccf.org.
Cleveland Clinic Lerner College of Medicine · USUniversity of Southern California · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
NCATS NIH HHS UL1 TR000439NCI NIH HHS P30 CA014089NCI NIH HHS P30CA014089
6 · The paper itself

Abstract

backgroundTherapeutic modalities effective in patients with progressive forms of multiple sclerosis (MS) are limited. In a murine model of progressive MS, the sustained disability during the chronic phase of experimental autoimmune encephalomyelitis (EAE) correlated with elevated expression of interleukin (IL)-6, a cytokine with pleiotropic functions and therapeutic target for non-central nervous system (CNS) autoimmune disease. Sustained IL-6 expression in astrocytes restricted to areas of demyelination suggested that IL-6 plays a major role in disease progression during chronic EAE.

methodsA progressive form of EAE was induced using transgenic mice expressing a dominant negative interferon-γ (IFN-γ) receptor alpha chain under control of human glial fibrillary acidic protein (GFAP) promoter (GFAPγR1Δ mice). The role of IL-6 in regulating progressive CNS autoimmunity was assessed by treating GFAPγR1Δ mice with anti-IL-6 neutralizing antibody during chronic EAE.

resultsIL-6 neutralization restricted disease progression and decreased disability, myelin loss, and axonal damage without affecting astrogliosis. IL-6 blockade reduced CNS inflammation by limiting inflammatory cell proliferation; however, the relative frequencies of CNS leukocyte infiltrates, including the Th1, Th17, and Treg CD4 T cell subsets, were not altered. IL-6 blockade rather limited the activation and proliferation of microglia, which correlated with higher expression of Galectin-1, a regulator of microglia activation expressed by astrocytes.

conclusionsThese data demonstrate that astrocyte-derived IL-6 is a key mediator of progressive disease and support IL-6 blockade as a viable intervention strategy to combat progressive MS.

Indexed as

Interleukin-6 InhibitorsAnimalsAntibodies, NeutralizingAstrocytesDemyelinating DiseasesEncephalomyelitis, Autoimmune, ExperimentalGlial Fibrillary Acidic ProteinGliosisHumansInterferon-gammaInterleukin-6Macrophage ActivationMiceMice, Inbred C57BLMice, TransgenicMicrogliaAntibodies, NeutralizingGlial Fibrillary Acidic ProteinInterferon-gammaInterleukin-6Interleukin-6 Inhibitors

Identifiers

PMID25896970
PMCPMC4410573
OpenAlexW2024688938

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.