Evidence map›Paper›PMID 29452810›Full record

ArticleBritish journal of anaesthesia2018

Interleukin-6 is both necessary and sufficient to produce perioperative neurocognitive disorder in mice.

J Hu, X Feng, M Valdearcos, D Lutrin, Y Uchida, S K Koliwad, M Maze

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of anaesthesia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04575753 (Evaluating the Role of Pre-existing Resolvins in the Resolution of ICU Delirium), which is not on this map. Cited by 91 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 1 pooled it
8.9field-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.

NCT04575753 withdrawnnot on this mapstarted 2023, after this paper: background citation

Evaluating the Role of Pre-existing Resolvins in the Resolution of ICU Delirium

TypeobservationalSponsorUniversité Libre de BruxellesRan2023 to 2024Enrolled0ConditionsDeliriumArmsStudy group
3 · Its place in the literature

Who cites it

91 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.

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31 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 2 institutions in 2 countries.

J HuDepartment of Anesthesia and Perioperative Care and Center for Cerebrovascular Research, University of California, San Francisco, CA, USA; Department of Anesthesia, Tongling People's Hospital, Tongling, Anhui 244000, People's Republic of China.
X FengDepartment of Anesthesia and Perioperative Care and Center for Cerebrovascular Research, University of California, San Francisco, CA, USA.
M ValdearcosThe Diabetes Center, University of California, San Francisco, CA, USA.
D LutrinDepartment of Anesthesia and Perioperative Care and Center for Cerebrovascular Research, University of California, San Francisco, CA, USA.
Y UchidaDepartment of Anesthesia and Perioperative Care and Center for Cerebrovascular Research, University of California, San Francisco, CA, USA.
S K KoliwadThe Diabetes Center, University of California, San Francisco, CA, USA.
M MazeDepartment of Anesthesia and Perioperative Care and Center for Cerebrovascular Research, University of California, San Francisco, CA, USA. Electronic address: mervyn.maze@ucsf.edu.
University of California, San Francisco · USThe People's Hospital Tongling · CN

Funding

Microglia: dietary fat-sensitive mediators of inflammation and metabolic diseaseR01DK103175 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KOLIWAD, SUNEIL KRISHNA · 2015 to 2019
$1.8M
Maladaptive Plasticity in Spinal Cord Injury: Cellular MechanismsR01NS088475 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERGUSON, ADAM R · 2015 to 2019
$1.7M
Cell type-specific influences on HHT pathogenesisR01HL122774 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SU, HUA · 2015 to 2018
$1.6M
Inflammation resolving mechanism dysregulation in postoperative cognitive declineR01GM104194 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MAZE, MERVYN · 2013 to 2016
$1.2M
NHLBI NIH HHS R01 HL122774NIDDK NIH HHS R01 DK103175NIGMS NIH HHS R01 GM104194NINDS NIH HHS R01 NS088475
6 · The paper itself

Abstract

backgroundPerioperative neurocognitive disorders (PND) result in long-term morbidity and mortality with no effective interventions available. Because interleukin-6 (IL-6), a pro-inflammatory cytokine, is consistently up-regulated by trauma, including after surgery, we determined whether IL-6 is a putative therapeutic target for PND in a mouse model.

methodsFollowing institutional approval, adult (12-14 weeks) male C57/Bl6 mice were pretreated with the IL-6 receptor (IL6R) blocking antibody tocilizumab prior to open tibia fracture with internal fixation under isoflurane anaesthesia. Inflammatory and behavioural responses in a trace fear conditioning (TFC) paradigm were assessed postoperatively. Separately, the effects of IL-6 administration or of depletion of bone marrow-derived monocytes (BM-DMs) with clodrolip on the inflammatory and behavioural responses were assessed. Blood brain barrier disruption, hippocampal microglial activation, and infiltration of BM-DMs were each assessed following IL-6 administration.

resultsThe surgery-induced decrement in freezing time in the TFC assay, indicative of cognitive decline, was attenuated by tocilizumab (P<0.01). The surgery-induced increase in pro-inflammatory mediators was significantly reduced by tocilizumab. Exogenously administered IL-6 significantly impaired freezing behaviour (P<0.05) and up-regulated pro-inflammatory cytokines; both responses were prevented by depletion of BM-DMs. IL-6 disrupted the blood brain barrier, and increased hippocampal activation of microglia and infiltration of BM-DMs.

conclusionsIL-6 is both necessary and sufficient to produce cognitive decline. Following further preclinical testing of its perioperative safety, the IL6R blocker tocilizumab is a candidate for prevention and/or treatment of PND.

Indexed as

Perioperative PeriodAnimalsBehavior, AnimalBlood-Brain BarrierDisease Models, AnimalHippocampusInterleukin-6MacrophagesMaleMiceMice, Inbred C57BLMicrogliaNeurocognitive DisordersInterleukin-6cognitive dysfunctioncytokinesinterleukin-6 (IL-6)surgerytocilizumab

Identifiers

PMID29452810
PMCPMC6200097
OpenAlexW2793292264

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.