Cytokine dysregulation persists in childhood post Neonatal Encephalopathy
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RESEARCH ARTICLE
Open Access
Cytokine dysregulation persists in childhood post Neonatal Encephalopathy Zunera Zareen1,2,3,4, Tammy Strickland1,2, Victoria Mc Eneaney1,2, Lynne A. Kelly1,2,5, Denise McDonald1,3, Deirdre Sweetman4 and Eleanor J. Molloy1,2,3,4,5,6*
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. Keywords: Cytokines, Neonatal encephalopathy, Inflammation, Neurodevelopmental, Hypoxic-ischaemic encephalopathy
Background Neonatal brain injury such as Neonatal encephalopathy (NE) is an important cause of neonatal death and disability such as cerebral palsy. Inflammation combined with Hypoxia-ischemia (HI) play an important pathophysiological role in NE. The injury processes can persist for months and years and a tertiary mechanism of damage has been proposed, which includes inflammation * Correspondence: [email protected] 1 Discipline of Paediatrics, Trinity College, The University of Dublin, Dublin, Ireland 2 Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland Full list of author information is available at the end of the article
and epigenetic changes [1], decreased plasticity and reduced number of neurons. Infants with NE have a persistent inflammatory response over the first week of life correlating with the degree of brain injury [2, 3]. Studies have shown that intermittent and sustained Inflammation demonstrated in preterm newborns may contribute to adverse neurodevelopmental outcome [4]. Pro-inflammatory cytokine expression within the brain, e
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