Cytokine dysregulation persists in childhood post Neonatal Encephalopathy

Background Cytokines are possible mediators of neuroinflammation and associated with adverse outcome in neonatal encephalopathy (NE). Our aim was to explore cytokine response in children with Neonatal Encephalopathy (NE) at school age compared to age-matched controls. Method Follow up at school age, children who had NE and age-matched controls were assessed for their cytokine responses and neurodevelopment outcome. Pro- and anti-inflammatory cytokines in the serum, [Interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-6, IL-8, IL-18, Tumor necrosis factor (TNF)-alpha, TNF beta, Interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), erythropoietin (EPO), IL-10 & IL-1RA] were measured at baseline and in response to in vitro stimulation with lipopolysaccharide (LPS: endotoxin). Results GM-CSF, TNF-beta, IL-2 IL-6 and IL-8 were significantly elevated at school age following NE (n = 40) compared to controls (n = 37). A rise in GM-CSF, IL-8, TNF-alpha, IL-1 beta, & IL-6 were seen in NE group following LPS stimulation. Relative LPS hypo-responsiveness was also noted in children with severe NE with IL-10, VEGF, EPO and TNF-beta. Elevated TNF-beta was associated with low gross motor scores on assessment at school age. Conclusion School-age children post-NE had significantly altered cytokine responses to endotoxin compared to controls. TNF-beta was associated with adverse developmental outcomes. This suggests the inflammatory process may persist into childhood and a longer therapeutic window may be available for neuroprotection therapies.