Cargando…

Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus

BACKGROUND: Neuroinflammation has been implicated in the pathophysiology of post-hemorrhagic hydrocephalus (PHH) of prematurity, but no comprehensive analysis of signaling molecules has been performed using human cerebrospinal fluid (CSF). METHODS: Lumbar CSF levels of key cytokines (IL-1α, IL-1β, I...

Descripción completa

Detalles Bibliográficos
Autores principales: Habiyaremye, Gakwaya, Morales, Diego M., Morgan, Clinton D., McAllister, James P., CreveCoeur, Travis S., Han, Rowland H., Gabir, Mohamed, Baksh, Brandon, Mercer, Deanna, Limbrick, David D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725948/
https://www.ncbi.nlm.nih.gov/pubmed/29228970
http://dx.doi.org/10.1186/s12987-017-0083-0
_version_ 1783285640862892032
author Habiyaremye, Gakwaya
Morales, Diego M.
Morgan, Clinton D.
McAllister, James P.
CreveCoeur, Travis S.
Han, Rowland H.
Gabir, Mohamed
Baksh, Brandon
Mercer, Deanna
Limbrick, David D.
author_facet Habiyaremye, Gakwaya
Morales, Diego M.
Morgan, Clinton D.
McAllister, James P.
CreveCoeur, Travis S.
Han, Rowland H.
Gabir, Mohamed
Baksh, Brandon
Mercer, Deanna
Limbrick, David D.
author_sort Habiyaremye, Gakwaya
collection PubMed
description BACKGROUND: Neuroinflammation has been implicated in the pathophysiology of post-hemorrhagic hydrocephalus (PHH) of prematurity, but no comprehensive analysis of signaling molecules has been performed using human cerebrospinal fluid (CSF). METHODS: Lumbar CSF levels of key cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF-β1, IFN-γ) and chemokines (XCL-1, CCL-2, CCL-3, CCL-19, CXCL-10, CXCL-11, CXCL-12) were measured using conventional and multiplexed Enzyme-linked Immunosorbent Assays and compared between preterm infants with PHH and those with no known neurological injury. The relationships between individual biomarker levels and specific CSF cell counts were examined. RESULTS: Total protein (TP) CSF levels were elevated in the PHH subjects compared to controls. CSF levels of IL-1α, IL-4, IL-6, IL-12, TNF-α, CCL-3, CCL-19, and CXCL-10 were significantly increased in PHH whereas XCL-1 was significantly decreased in PHH. When normalizing by TP, IL-1α, IL-1β, IL-10, IL-12, CCL-3, and CCL-19 levels were significantly elevated compared to controls, while XCL-1 levels remained significantly decreased. Among those with significantly different levels in both absolute and normalized levels, only absolute CCL-19 levels showed a significant correlation with CSF nucleated cells, neutrophils, and lymphocytes. IL-1β and CXCL-10 also were correlated with total cell count, nucleated cells, red blood cells, and neutrophils. CONCLUSIONS: Neuroinflammation is likely to be an important process in the pathophysiology of PHH. To our knowledge, this is the first study to investigate CSF levels of chemokines in PHH as well as the only one to show XCL-1 selectively decreased in a diseased state. Additionally, CCL-19 was the only analyte studied that showed significant differences between groups and had significant correlation with cell count analysis. The selectivity of CCL-19 and XCL-1 should be further investigated. Future studies will further delineate the role of these cytokines and chemokines in PHH.
format Online
Article
Text
id pubmed-5725948
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-57259482017-12-13 Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus Habiyaremye, Gakwaya Morales, Diego M. Morgan, Clinton D. McAllister, James P. CreveCoeur, Travis S. Han, Rowland H. Gabir, Mohamed Baksh, Brandon Mercer, Deanna Limbrick, David D. Fluids Barriers CNS Research BACKGROUND: Neuroinflammation has been implicated in the pathophysiology of post-hemorrhagic hydrocephalus (PHH) of prematurity, but no comprehensive analysis of signaling molecules has been performed using human cerebrospinal fluid (CSF). METHODS: Lumbar CSF levels of key cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF-β1, IFN-γ) and chemokines (XCL-1, CCL-2, CCL-3, CCL-19, CXCL-10, CXCL-11, CXCL-12) were measured using conventional and multiplexed Enzyme-linked Immunosorbent Assays and compared between preterm infants with PHH and those with no known neurological injury. The relationships between individual biomarker levels and specific CSF cell counts were examined. RESULTS: Total protein (TP) CSF levels were elevated in the PHH subjects compared to controls. CSF levels of IL-1α, IL-4, IL-6, IL-12, TNF-α, CCL-3, CCL-19, and CXCL-10 were significantly increased in PHH whereas XCL-1 was significantly decreased in PHH. When normalizing by TP, IL-1α, IL-1β, IL-10, IL-12, CCL-3, and CCL-19 levels were significantly elevated compared to controls, while XCL-1 levels remained significantly decreased. Among those with significantly different levels in both absolute and normalized levels, only absolute CCL-19 levels showed a significant correlation with CSF nucleated cells, neutrophils, and lymphocytes. IL-1β and CXCL-10 also were correlated with total cell count, nucleated cells, red blood cells, and neutrophils. CONCLUSIONS: Neuroinflammation is likely to be an important process in the pathophysiology of PHH. To our knowledge, this is the first study to investigate CSF levels of chemokines in PHH as well as the only one to show XCL-1 selectively decreased in a diseased state. Additionally, CCL-19 was the only analyte studied that showed significant differences between groups and had significant correlation with cell count analysis. The selectivity of CCL-19 and XCL-1 should be further investigated. Future studies will further delineate the role of these cytokines and chemokines in PHH. BioMed Central 2017-12-12 /pmc/articles/PMC5725948/ /pubmed/29228970 http://dx.doi.org/10.1186/s12987-017-0083-0 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Habiyaremye, Gakwaya
Morales, Diego M.
Morgan, Clinton D.
McAllister, James P.
CreveCoeur, Travis S.
Han, Rowland H.
Gabir, Mohamed
Baksh, Brandon
Mercer, Deanna
Limbrick, David D.
Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus
title Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus
title_full Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus
title_fullStr Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus
title_full_unstemmed Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus
title_short Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus
title_sort chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725948/
https://www.ncbi.nlm.nih.gov/pubmed/29228970
http://dx.doi.org/10.1186/s12987-017-0083-0
work_keys_str_mv AT habiyaremyegakwaya chemokineandcytokinelevelsinthelumbarcerebrospinalfluidofpreterminfantswithposthemorrhagichydrocephalus
AT moralesdiegom chemokineandcytokinelevelsinthelumbarcerebrospinalfluidofpreterminfantswithposthemorrhagichydrocephalus
AT morganclintond chemokineandcytokinelevelsinthelumbarcerebrospinalfluidofpreterminfantswithposthemorrhagichydrocephalus
AT mcallisterjamesp chemokineandcytokinelevelsinthelumbarcerebrospinalfluidofpreterminfantswithposthemorrhagichydrocephalus
AT crevecoeurtraviss chemokineandcytokinelevelsinthelumbarcerebrospinalfluidofpreterminfantswithposthemorrhagichydrocephalus
AT hanrowlandh chemokineandcytokinelevelsinthelumbarcerebrospinalfluidofpreterminfantswithposthemorrhagichydrocephalus
AT gabirmohamed chemokineandcytokinelevelsinthelumbarcerebrospinalfluidofpreterminfantswithposthemorrhagichydrocephalus
AT bakshbrandon chemokineandcytokinelevelsinthelumbarcerebrospinalfluidofpreterminfantswithposthemorrhagichydrocephalus
AT mercerdeanna chemokineandcytokinelevelsinthelumbarcerebrospinalfluidofpreterminfantswithposthemorrhagichydrocephalus
AT limbrickdavidd chemokineandcytokinelevelsinthelumbarcerebrospinalfluidofpreterminfantswithposthemorrhagichydrocephalus