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Distinct cytokines are related to the severity of perinatal asphyxia in the neonate – an observational study

Presented at the Neonatal Society 2016 Autumn Meeting.

Bajnok A, Berta L, Orbán C, Tulassay T, Toldi G

First Department of Pediatrics, Semmelweis University, Budapest, Hungary

Background: Neuroinflammation and a systemic inflammatory response are important features of perinatal asphyxia. The neuroinflammatory response may have dual aspects in being a hindrance on the one hand but also a significant help on the other for the recovery of the CNS. We aimed to assess intracellular cytokine levels of T lymphocytes and plasma cytokine levels in moderate and severe perinatal asphyxia in order to identify players of the inflammatory response that may influence patient outcome.

Methods: We analyzed data of 29 term neonates requiring moderate systemic hypothermia in a single-centre observational study in Budapest, Hungary, approved by an independent ethical committee of the institution. Venous blood samples were collected between 3-6 hours, at 24 hours, 3 days, 1 week and 1 month of life. Peripheral blood mononuclear cells were stained with fluorescent-conjugated antibodies for intracellular cytokines and cell surface markers and analysed by flow cytometry. Cytokine plasma levels were measured using Bioplex immunoassays. Data were analyzed using non-parametrical statistics.

Results: Neonates were divided into a moderate (n = 18) and a severe (n = 11) group based on masked MRI neuroradiological findings. The prevalence of IL-1b-expressing CD4 cells was higher in severe than in moderate asphyxia at 6 hrs (6.77 (3.18-10.26) % vs 3.52 (2.13-5.16) %, p = 0.02). Plasma and intracellular levels of IL-1b were highest at 6 hrs in both groups. Intracellular levels of TNF-a in CD4 cells were increased at all time points compared to 6 hrs in both groups. At 1 month, intracellular levels of TNF-a were higher in the severe group (4729 (3959-6714) MFI vs 3281 (1752-4326) MFI, p = 0.03). Plasma IL-6 levels were higher at 1 week in the severe group (70.25 (33.73-134.1) pg/ml vs 21.06 (11.89-43.24) pg/ml, p = 0.001) and decreased by 1 month following the insult in the moderate group. Intracellular levels of IL-6 peaked at 24 hours in both groups. Intracellular TGF-b levels were increased from 24 hours onwards in the moderate group.

Conclusion: IL-1b and IL-6 appear to play a key role in the early events of the inflammatory response, while TNF-a seems to be responsible for prolonged neuroinflammation, potentially contributing to a worse outcome in perinatal asphyxia. TGF-b has a compensatory role in decreasing inflammation from an early stage following the insult.

Corresponding author: toldigergely@yahoo.com

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