Association of Brain Injury and Neonatal Cytokine Response during Therapeutic Hypothermia (TH) in Newborns with Hypoxic-Ischemic Encephalopathy (HIE)

BACKGROUND: Cytokines have been proposed as mediators of neonatal brain injury via neuroinflammatory pathways triggered by hypoxia-ischemia. Limited data are available on cytokine profiles in larger cohorts of newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). METHODS: Serum cytokines IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, TNF-α, IFN-γ were measured in newborns with HIE at 24 and 72 hours of TH. Differences between infants with favorable (survivors with mild/no MRI injury) versus adverse outcome (death or moderate/severe MRI injury) were compared using mixed models to adjust for covariates. RESULTS: Data from 36 term newborns with HIE (favorable outcome: n=20, adverse outcome: n=16) were evaluated. Cytokines IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-13 were elevated in the adverse relative to favorable outcome group at 24 hours. IL-6 remained significantly elevated in the adverse outcome group at 72 hours. IL-6 and IL-10 remained significantly associated with outcome group after controlling for covariates. CONCLUSION: Inflammatory cytokines are elevated in HIE newborns with brain injury by MRI. In particular, IL-6 and IL-10 were associated with adverse outcomes after controlling for baseline characteristics and severity of presentation. These data suggest that cytokine response may identify infants in need of additional neuroprotective interventions.