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-1â+ and CD4+ IL-1â+ 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-á in CD4 cells were increased at all time points compared to 6 h in both groups. At 1 month, intracellular levels of TNF-á 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-â levels were increased from 24 h onwards in the moderate group.CONCLUSIONS: IL-1â and IL-6 appear to play a key role in the early events of the inflammatory response, while TNF-á seems to be responsible for prolonged neuroinflammation, potentially contributing to a worse outcome. The assessment of the prevalence of CD4+ IL-1â+ and CD4+ IL-1â+ CD49d+ cells at 6 h appears to be able to predict the severity of the insult at an early stage in asphyxia.
Asphyxia Neonatorum Cytokines