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Cytokine production pattern of T lymphocytes in neonatal arterial ischaemic stroke during the first month of life – a case series

Presented at the Neonatal Society 2018 Summer Meeting (programme).

Bajnok A1,2, Berta L2, Orbán C2, Tulassay T2, Toldi G1,2,3

1 First Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
2 First Department of Pediatrics, Semmelweis University, Budapest, Hungary
3 Birmingham Women’s and Children’s Hospital, Neonatal Unit, Birmingham, UK

Background: The perinatal period carries the highest risk for stroke in childhood, however the pathophysiology is poorly understood. A new pathophysiological model describes the development of neonatal arterial ischemic stroke (NAIS) as the combined result of prenatal inflammation and hypoxic–ischemic insult. Neuroinflammation and a systemic inflammatory response are also important features of NAIS. Identifying key players of the inflammatory system is in the limelight of current research.

Methods: We present four NAIS cases, in whom detailed analysis of intracellular and plasma cytokine levels are available from the first month of life. All neonates were admitted for cooling with the initial diagnosis of hypoxic-ischemic encephalopathy (HIE), however, early MRI examination revealed NAIS. Blood samples were collected between 3-6 h of life, at 24 h, 72 h, 1 week and 1 month of life. Peripheral blood mononuclear cells were assessed with flow cytometry and plasma cytokine levels were measured as described earlier (1). Pooled data from the cohort of 4 NAIS patients were compared to infants with HIE.

Results: At 6 and 72 h of age the prevalence of IL10+ CD8+ lymphocytes remained lower in NAIS. At 6 h CD8+ lymphocytes produced more IL-17 in NAIS than in HIE. At 72 h CD8+ cells produced more IL-6 in severe HIE than in NAIS, but IL-6 production remained elevated in CD8 cells at 1 month in NAIS, while it decreased in HIE. At 1 week the prevalence of TGFβ+ lymphocytes prone to enter the CNS was elevated in NAIS. On the other hand, by 1 month of age the prevalence of TGFβ+ CD4+ lymphocytes decreased in NAIS compared to HIE. At 72 h we found elevated plasma levels of IL-5, MCP-1 and IL-17 in NAIS. By 1 month, plasma levels of IL-4, IL-12 and IL-17 decreased in NAIS but remained elevated in HIE.

Conclusion: Differences in the cytokine network are present between NAIS and HIE. CD8 lymphocytes appear to shift towards the pro-inflammatory direction in NAIS. The inflammatory response appears to be more pronounced at 72 h in NAIS but decreases faster, reaching lower plasma levels of inflammatory markers at 1 month.

Corresponding author:

1. Bajnok A et al. Distinct cytokine patterns may regulate the severity of neonatal asphyxia - an observational study. J Neuroinflammation 2017,14:244.

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