Cytokine Dysregulation Persists in Childhood Post Neonatal Encephalopathy

• DOI: 10.21203/rs.2.16375/v3
• Publication Date: 2020-02-24T16:51:48Z
• Authors: Zunera Zareen; Tammy Strickland; Victoria Mc Eneaney; Lynne A. Kelly; Denise McDonald; Deirdre Sweetman; Eleanor J. Molloy
• Keywords: Inflammation; Male; Asphyxia Neonatorum; Brain Diseases; Hypoxic-ischaemic encephalopathy; Infant, Newborn; Neonatal encephalopathy; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Neurodevelopmental Disorders; Neurodevelopmental; Cytokines; Humans; Female; Neurology. Diseases of the nervous system; RC346-429; Child; Research Article

Abstract 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)-1α, IL-1β, IL-2, IL-6, IL-8, IL-18, Tumor necrosis factor (TNF)-α, TNF β, Interferon (IFN)-γ, 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-β, 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-α, IL-1β, & 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-β. Elevated TNF-β 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-β 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.