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Published on: November 20, 2015
Cytokine dysregulation persists in childhood post Neonatal Encephalopathy
Zunera Zareen1,2,3,4, Tammy Strickland1,2, Victoria Mc Eneaney1,2
1Discipline of Paediatrics, Trinity College, The University of Dublin, Dublin, Ireland.
Insights
Children with neonatal encephalopathy (NE) show altered cytokine responses at school age, with elevated levels of certain cytokines like TNF-β linked to poorer motor skills. This suggests persistent inflammation and potential for neuroprotection therapies.
Area of Science:
- Neuroscience
- Immunology
- Pediatrics
Background:
- Neonatal encephalopathy (NE) is linked to neuroinflammation and adverse outcomes.
- Cytokine profiles may serve as biomarkers for NE-associated neuroinflammation.
- Understanding long-term cytokine responses in NE is crucial for predicting neurodevelopmental trajectories.
Purpose of the Study:
- To investigate and compare cytokine responses in school-aged children with a history of NE versus age-matched controls.
- To assess the correlation between cytokine profiles and neurodevelopmental outcomes at school age.
Main Methods:
- School-age follow-up of children with NE and controls.
- Measurement of serum pro- and anti-inflammatory cytokines (e.g., IL-1α, IL-6, TNF-α, GM-CSF) at baseline and after in vitro lipopolysaccharide (LPS) stimulation.
- Neurodevelopmental assessment, including gross motor skills.
Main Results:
- Significantly elevated serum cytokines (GM-CSF, TNF-β, IL-2, IL-6, IL-8) were observed in school-aged children post-NE compared to controls.
- NE group showed increased cytokine production (GM-CSF, IL-8, TNF-α, IL-1β, IL-6) post-LPS stimulation.
- Children with severe NE exhibited relative LPS hypo-responsiveness (IL-10, VEGF, EPO, TNF-β).
- Elevated TNF-β levels correlated with lower gross motor scores.
Conclusions:
- Children with a history of NE exhibit distinct cytokine responses to endotoxin stimulation at school age.
- Persistent inflammation and altered immune responses may contribute to long-term neurodevelopmental deficits.
- Findings suggest a potential for extended therapeutic windows for neuroprotection strategies in NE survivors.
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.
