Changes in serum cytokine and cortisol levels in normothermic and hypothermic term neonates after perinatal asphyxia

Abstract

OBJECTIVE: Perinatal asphyxia is characterized by an inflammatory response that contributes to cerebral injury. Therapeutic hypothermia improves neurological outcome in asphyxiated term neonates, but its clear effect on the inflammatory response is unknown. SUBJECTS AND METHODS: A range of cytokines and cortisol levels were measured at the 6th, 12th and 24th postnatal hours in neonates with hypoxic-ischemic encephalopathy treated with standard intensive care on hypothermia (n = 10) or normothermia (n = 8). The influence of postnatal age and hypothermia on serum cytokine and cortisol levels was evaluated. RESULTS: Interleukin (IL)-6 levels (at 6 h of age) and IL-4 levels (at all time points) were significantly lower in asphyxiated neonates treated with hypothermia compared to normothermic neonates. Vascular endothelial growth factor levels were higher in the hypothermia than in the normothermia group at the 6th and 12th postnatal hours. IL-10 levels decreased significantly between 6 and 24 h of age in both groups. However, no difference of IL-10 levels was observed between the study groups. The duration of hypothermia before 6 hours of age correlated with lower levels of IL-6, interferon-gamma and tumor necrosis factor-alpha measured at 6 h of age and IL-10 levels at 12 h of age. Cortisol levels did not differ between the study groups, but did gradually decrease in both groups during the study period. At 6 and 24 h of age, a positive correlation was observed between cortisol and IL-10 levels. CONCLUSIONS: Therapeutic hypothermia may rapidly suppress and modify the immediate cytokine response to asphyxia. The correlation between cytokine levels and duration of hypothermia suggests that the earlier hypothermia is introduced, the more pronounced its beneficial immunomodulatory effect.