Interleukin-8 dysregulation is implicated in brain dysmaturation following preterm birth.


Journal

Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478

Informations de publication

Date de publication:
11 2020
Historique:
received: 20 05 2020
revised: 05 09 2020
accepted: 05 09 2020
pubmed: 14 9 2020
medline: 28 4 2021
entrez: 13 9 2020
Statut: ppublish

Résumé

Preterm birth is associated with dysconnectivity of structural brain networks, impaired cognition and psychiatric disease. Systemic inflammation contributes to cerebral dysconnectivity, but the immune mediators driving this association are poorly understood. We analysed information from placenta, umbilical cord and neonatal blood, and brain MRI to determine which immune mediators link perinatal systemic inflammation with dysconnectivity of structural brain networks. Participants were 102 preterm infants (mean gestational age 29 HCA was associated with elevated concentrations of C5a, C9, CRP, IL-1β, IL-6, IL-8 and MCP-1 in cord blood, and IL-8 concentration predicted HCA with an area under the receiver operator curve of 0.917 (95% CI 0.841 - 0.993, p < 0.001). Fourteen analytes explained 66% of the variance in the postnatal profile (BDNF, C3, C5a, C9, CRP, IL-1β, IL-6, IL-8, IL-18, MCP-1, MIP-1β, MMP-9, RANTES and TNF-α). Of these, IL-8 was associated with altered neurite density index across the white matter skeleton after adjustment for gestational age at birth and at scan (β = 0.221, p = 0.037). These findings suggest that IL-8 dysregulation has a role in linking perinatal systemic inflammation and atypical white matter development in preterm infants.

Sections du résumé

BACKGROUND
Preterm birth is associated with dysconnectivity of structural brain networks, impaired cognition and psychiatric disease. Systemic inflammation contributes to cerebral dysconnectivity, but the immune mediators driving this association are poorly understood. We analysed information from placenta, umbilical cord and neonatal blood, and brain MRI to determine which immune mediators link perinatal systemic inflammation with dysconnectivity of structural brain networks.
METHODS
Participants were 102 preterm infants (mean gestational age 29
RESULTS
HCA was associated with elevated concentrations of C5a, C9, CRP, IL-1β, IL-6, IL-8 and MCP-1 in cord blood, and IL-8 concentration predicted HCA with an area under the receiver operator curve of 0.917 (95% CI 0.841 - 0.993, p < 0.001). Fourteen analytes explained 66% of the variance in the postnatal profile (BDNF, C3, C5a, C9, CRP, IL-1β, IL-6, IL-8, IL-18, MCP-1, MIP-1β, MMP-9, RANTES and TNF-α). Of these, IL-8 was associated with altered neurite density index across the white matter skeleton after adjustment for gestational age at birth and at scan (β = 0.221, p = 0.037).
CONCLUSIONS
These findings suggest that IL-8 dysregulation has a role in linking perinatal systemic inflammation and atypical white matter development in preterm infants.

Identifiants

pubmed: 32920182
pii: S0889-1591(20)31018-7
doi: 10.1016/j.bbi.2020.09.007
pii:
doi:

Substances chimiques

Interleukin-8 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

311-318

Subventions

Organisme : Medical Research Council
ID : MR/N022556/1
Pays : United Kingdom
Organisme : The Dunhill Medical Trust
ID : R380R/1114
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1002033
Pays : United Kingdom

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Gemma Sullivan (G)

MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.

Paola Galdi (P)

MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.

Manuel Blesa Cabez (MB)

MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.

Nis Borbye-Lorenzen (N)

Danish Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.

David Q Stoye (DQ)

MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.

Gillian J Lamb (GJ)

MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.

Margaret J Evans (MJ)

Department of Pathology, Royal Infirmary of Edinburgh, Edinburgh, UK.

Alan J Quigley (AJ)

Department of Radiology, Royal Hospital for Sick Children, Edinburgh, UK.

Michael J Thrippleton (MJ)

Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; Edinburgh Imaging, University of Edinburgh, Edinburgh, UK.

Kristin Skogstrand (K)

Danish Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.

Siddharthan Chandran (S)

Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; MRC Centre for Regenerative Medicine, University of Edinburgh, UK.

Mark E Bastin (ME)

Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.

James P Boardman (JP)

MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. Electronic address: james.boardman@ed.ac.uk.

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