Distinct cytokine patterns may regulate the severity of neonatal asphyxia-an observational study

Anna Bajnok, László Berta, Csaba Orbán, G. Veres, Dénes Zádori, Hajnalka Barta, Ünoke Méder, L. Vécsei, T. Tulassay, M. Szabó, Gergely Toldi

Research output: Contribution to journalArticle

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Abstract

Background: Neuroinflammation and a systemic inflammatory reaction are important features of perinatal asphyxia. Neuroinflammation may have dual aspects being a hindrance, but also a significant help in the recovery of the CNS. We aimed to assess intracellular cytokine levels of T-lymphocytes and plasma cytokine levels in moderate and severe asphyxia in order to identify players of the inflammatory response that may influence patient outcome. Methods: We analyzed the data of 28 term neonates requiring moderate systemic hypothermia in a single-center observational study. Blood samples were collected between 3 and 6 h of life, at 24 h, 72 h, 1 week, and 1 month of life. Neonates were divided into a moderate (n=17) and a severe (n=11) group based on neuroradiological and amplitude-integrated EEG characteristics. Peripheral blood mononuclear cells were assessed with flow cytometry. Cytokine plasma levels were measured using Bioplex immunoassays. Components of the kynurenine pathway were assessed by high-performance liquid chromatography. Results: The prevalence and extravasation of IL-1b + CD4 cells were higher in severe than in moderate asphyxia at 6 h. Based on Receiver operator curve analysis, the assessment of the prevalence of CD4+ IL-1β+ and CD4+ IL-1β+ CD49d+ cells at 6 h appears to be able to predict the severity of the insult at an early stage in asphyxia. Intracellular levels of TNF-α in CD4 cells were increased at all time points compared to 6 h in both groups. At 1 month, intracellular levels of TNF-α were higher in the severe group. Plasma IL-6 levels were higher at 1 week in the severe group and decreased by 1 month in the moderate group. Intracellular levels of IL-6 peaked at 24 h in both groups. Intracellular TGF-β levels were increased from 24 h onwards in the moderate group. Conclusions: IL-1β and IL-6 appear to play a key role in the early events of the inflammatory response, while TNF-α seems to be responsible for prolonged neuroinflammation, potentially contributing to a worse outcome. The assessment of the prevalence of CD4+ IL-1β+ and CD4+ IL-1β+ CD49d+ cells at 6 h appears to be able to predict the severity of the insult at an early stage in asphyxia.

Original languageEnglish
Article number244
JournalJournal of Neuroinflammation
Volume14
Issue number1
DOIs
Publication statusPublished - Dec 12 2017

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Asphyxia
Interleukin-1
Observational Studies
Cytokines
Interleukin-6
Newborn Infant
Kynurenine
Hypothermia
Immunoassay
Electroencephalography
Blood Cells
Flow Cytometry
High Pressure Liquid Chromatography
T-Lymphocytes

Keywords

  • Cytokine network
  • Hypoxic ischemic encephalopathy
  • Neuroinflammation
  • Perinatal asphyxia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Distinct cytokine patterns may regulate the severity of neonatal asphyxia-an observational study. / Bajnok, Anna; Berta, László; Orbán, Csaba; Veres, G.; Zádori, Dénes; Barta, Hajnalka; Méder, Ünoke; Vécsei, L.; Tulassay, T.; Szabó, M.; Toldi, Gergely.

In: Journal of Neuroinflammation, Vol. 14, No. 1, 244, 12.12.2017.

Research output: Contribution to journalArticle

Bajnok, Anna ; Berta, László ; Orbán, Csaba ; Veres, G. ; Zádori, Dénes ; Barta, Hajnalka ; Méder, Ünoke ; Vécsei, L. ; Tulassay, T. ; Szabó, M. ; Toldi, Gergely. / Distinct cytokine patterns may regulate the severity of neonatal asphyxia-an observational study. In: Journal of Neuroinflammation. 2017 ; Vol. 14, No. 1.
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AU - Berta, László

AU - Orbán, Csaba

AU - Veres, G.

AU - Zádori, Dénes

AU - Barta, Hajnalka

AU - Méder, Ünoke

AU - Vécsei, L.

AU - Tulassay, T.

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AU - Toldi, Gergely

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N2 - Background: Neuroinflammation and a systemic inflammatory reaction are important features of perinatal asphyxia. Neuroinflammation may have dual aspects being a hindrance, but also a significant help in the recovery of the CNS. We aimed to assess intracellular cytokine levels of T-lymphocytes and plasma cytokine levels in moderate and severe asphyxia in order to identify players of the inflammatory response that may influence patient outcome. Methods: We analyzed the data of 28 term neonates requiring moderate systemic hypothermia in a single-center observational study. Blood samples were collected between 3 and 6 h of life, at 24 h, 72 h, 1 week, and 1 month of life. Neonates were divided into a moderate (n=17) and a severe (n=11) group based on neuroradiological and amplitude-integrated EEG characteristics. Peripheral blood mononuclear cells were assessed with flow cytometry. Cytokine plasma levels were measured using Bioplex immunoassays. Components of the kynurenine pathway were assessed by high-performance liquid chromatography. Results: The prevalence and extravasation of IL-1b + CD4 cells were higher in severe than in moderate asphyxia at 6 h. Based on Receiver operator curve analysis, the assessment of the prevalence of CD4+ IL-1β+ and CD4+ IL-1β+ CD49d+ cells at 6 h appears to be able to predict the severity of the insult at an early stage in asphyxia. Intracellular levels of TNF-α in CD4 cells were increased at all time points compared to 6 h in both groups. At 1 month, intracellular levels of TNF-α were higher in the severe group. Plasma IL-6 levels were higher at 1 week in the severe group and decreased by 1 month in the moderate group. Intracellular levels of IL-6 peaked at 24 h in both groups. Intracellular TGF-β levels were increased from 24 h onwards in the moderate group. Conclusions: IL-1β and IL-6 appear to play a key role in the early events of the inflammatory response, while TNF-α seems to be responsible for prolonged neuroinflammation, potentially contributing to a worse outcome. The assessment of the prevalence of CD4+ IL-1β+ and CD4+ IL-1β+ CD49d+ cells at 6 h appears to be able to predict the severity of the insult at an early stage in asphyxia.

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