Zunera Zareen1,2,3,4, Tammy Strickland1,2, Victoria Mc Eneaney1,2, Lynne A Kelly1,2,5, Denise McDonald1,3, Deirdre Sweetman4, Eleanor J Molloy6,7,8,9,10,11. 1. Discipline of Paediatrics, Trinity College, The University of Dublin, Dublin, Ireland. 2. Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland. 3. Paediatrics, Children's Hospital Ireland (CHI) at Tallaght University Hospital, Dublin, 24, Ireland. 4. Paediatrics, National Maternity Hospital, Holles Street, Dublin, Ireland. 5. Paediatrics, Coombe Women and Infants University Hospital, Dublin, Ireland. 6. Discipline of Paediatrics, Trinity College, The University of Dublin, Dublin, Ireland. elesean@hotmail.com. 7. Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland. elesean@hotmail.com. 8. Paediatrics, Children's Hospital Ireland (CHI) at Tallaght University Hospital, Dublin, 24, Ireland. elesean@hotmail.com. 9. Paediatrics, National Maternity Hospital, Holles Street, Dublin, Ireland. elesean@hotmail.com. 10. Paediatrics, Coombe Women and Infants University Hospital, Dublin, Ireland. elesean@hotmail.com. 11. Neonatology, CHI at Crumlin, Dublin, Ireland. elesean@hotmail.com.
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.
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.
Authors: Yuma Kitase; Eric M Chin; Sindhu Ramachandra; Christopher Burkhardt; Nethra K Madurai; Colleen Lenz; Alexander H Hoon; Shenandoah Robinson; Lauren L Jantzie Journal: J Neuroinflammation Date: 2021-10-19 Impact factor: 8.322
Authors: Elina J Rancken; Marjo P H Metsäranta; Mika Gissler; Leena K Rahkonen; Leena M Haataja Journal: Pediatr Res Date: 2021-08-31 Impact factor: 3.953
Authors: Raymand Pang; Brian M Mujuni; Kathryn A Martinello; Emily L Webb; Angela Nalwoga; Julius Ssekyewa; Margaret Musoke; Jennifer J Kurinczuk; Margaret Sewegaba; Frances M Cowan; Stephen Cose; Margaret Nakakeeto; Alison M Elliott; Neil J Sebire; Nigel Klein; Nicola J Robertson; Cally J Tann Journal: Pediatr Res Date: 2021-03-05 Impact factor: 3.953