Association of brain injury and neonatal cytokine response during therapeutic hypothermia in newborns with hypoxic-ischemic encephalopathy

Pediatr Res. 2016 May;79(5):742-7. doi: 10.1038/pr.2015.280. Epub 2015 Dec 30.

Abstract

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 interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-α, and interferon-γ were measured in newborns with HIE at 24 and 72 h of TH. Differences between infants with favorable (survivors with mild/no magnetic resonance imaging (MRI) injury) vs. 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 h. IL-6 remained significantly elevated in the adverse outcome group at 72 h. 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Brain Injuries / blood*
  • Cohort Studies
  • Cytokines / blood
  • Cytokines / metabolism*
  • Female
  • Gestational Age
  • Humans
  • Hypothermia, Induced*
  • Hypoxia-Ischemia, Brain / blood*
  • Hypoxia-Ischemia, Brain / therapy*
  • Infant, Newborn
  • Inflammation
  • Magnetic Resonance Imaging
  • Male
  • Time Factors

Substances

  • Cytokines