Systemic inflammation alters the neuroinflammatory response: a prospective clinical trial in traumatic brain injury.
Cytokines
Human
IL1-ra
Infection
Inflammation
Neuroinflammation
Traumatic brain injury
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
25 Sep 2021
25 Sep 2021
Historique:
received:
13
05
2021
accepted:
30
08
2021
entrez:
26
9
2021
pubmed:
27
9
2021
medline:
1
2
2022
Statut:
epublish
Résumé
Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development; however, how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition. TBI patients recruited to a previous randomised controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n = 10 treatment arm, n = 10 control arm). Cytokine concentrations were measured in arterial and jugular venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 h. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used. Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen. No substantial delayed temporal associations between blood and brain compartments were detected. The development of a systemic clinical infection resulted in a significant decrease of IL1-ra, G-CSF, PDGF-ABBB, MIP-1b and RANTES (p < 0.05, respectively) in brain-ECF, even if adjusting for injury severity and demographic factors, while an increase in several cytokines could be seen in arterial blood. Systemic inflammation, and infection in particular, alters cytokine levels with different patterns seen in brain and in blood. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, but novel prospective trials are warranted to confirm these associations.
Sections du résumé
BACKGROUND
BACKGROUND
Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development; however, how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition.
METHODS
METHODS
TBI patients recruited to a previous randomised controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n = 10 treatment arm, n = 10 control arm). Cytokine concentrations were measured in arterial and jugular venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 h. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used.
RESULTS
RESULTS
Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen. No substantial delayed temporal associations between blood and brain compartments were detected. The development of a systemic clinical infection resulted in a significant decrease of IL1-ra, G-CSF, PDGF-ABBB, MIP-1b and RANTES (p < 0.05, respectively) in brain-ECF, even if adjusting for injury severity and demographic factors, while an increase in several cytokines could be seen in arterial blood.
CONCLUSIONS
CONCLUSIONS
Systemic inflammation, and infection in particular, alters cytokine levels with different patterns seen in brain and in blood. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, but novel prospective trials are warranted to confirm these associations.
Identifiants
pubmed: 34563211
doi: 10.1186/s12974-021-02264-2
pii: 10.1186/s12974-021-02264-2
pmc: PMC8464153
doi:
Substances chimiques
Cytokines
0
Immunomodulating Agents
0
Interleukin 1 Receptor Antagonist Protein
0
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
221Subventions
Organisme : Medical Research Council
ID : MR/R005036/1
Pays : United Kingdom
Organisme : MRC Grant
ID : MR/R005036/1
Organisme : Medical Research Council
ID : G0802251
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0600986
Pays : United Kingdom
Organisme : NIHR Global Health Research Group on Neurotrauma a European Union Seventh Framework Program grant (Collaborative European NeuroTrauma Effectiveness Research in TBI [CENTER-TBI])
ID : 602150
Organisme : MRC/Royal of Surgeons of England Clinical Research Training Fellowship
ID : G0802251
Informations de copyright
© 2021. The Author(s).
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