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Cytokine dysregulation in children with cerebral palsy
Zunera Zareen1,2,3,4, Tammy Strickland1,2, Lida Fallah2,5
1Discipline of Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland.
Insights
Children with cerebral palsy (CP) show altered inflammatory responses, with elevated erythropoietin and reduced responses to lipopolysaccharide (LPS) for key cytokines, indicating a persistent altered inflammatory state.
Area of Science:
- Immunology
- Pediatrics
- Neuroscience
Background:
- Children with cerebral palsy (CP) may exhibit altered immune responses.
- Understanding cytokine profiles in CP is crucial for identifying potential therapeutic targets.
Purpose of the Study:
- To investigate pro- and anti-inflammatory cytokine levels in children with CP.
- To assess immune response to endotoxin (lipopolysaccharide) in CP.
- To compare cytokine profiles and immune responses with age-matched controls.
Main Methods:
- Serum cytokines were analyzed in 12 children with CP and 12 age-matched controls.
- Multiplex enzyme-linked immunosorbent assay measured 14 cytokines at baseline and after lipopolysaccharide stimulation.
- Cytokines included interleukins, tumor necrosis factors, and growth factors.
Main Results:
- Children with CP had significantly higher baseline erythropoietin levels.
- Both groups showed strong responses to lipopolysaccharide for IL-8, VEGF, TNF-α, and GM-CSF.
- Children with CP exhibited hyporesponsiveness to lipopolysaccharide for IL-1α, IL-1β, IL-2, and IL-6.
Conclusions:
- Altered inflammatory responses and cytokine profiles persist in children with CP.
- Elevated erythropoietin and reduced inflammatory cytokine response to LPS in CP suggest an altered immune state.
- These findings may indicate potential therapeutic targets for managing CP sequelae.
Aim:
To examine pro- and anti-inflammatory cytokines in children with cerebral palsy (CP) at baseline and in response to endotoxin (lipopolysaccharide), and correlate outcomes compared with age-matched comparisons, to evaluate their ability to mount an immune response.
Method:
Serum cytokines were assessed in 12 children (eight males, four females; mean age 10y 1mo [SD 1y 8mo], 6-16y) with CP against 12 age-matched comparisons (eight males, four females; mean age 9y 1mo [SD 1y 1mo]). Pro- and anti-inflammatory cytokines (interleukin-1β, interleukin-2, interleukin-6, interleukin-8, interleukin-10, interleukin-18, tumour necrosis factor [TNF]-α, TNF-β, interferon-γ, granulocyte-macrophage colony-stimulating factor [GM-CSF], vascular endothelial growth factor [VEGF], erythropoietin, and interleukin-1 receptor antagonist) were measured at baseline and in response to in vitro simulation with lipopolysaccharide by multiplex enzyme-linked immunosorbent assay.
Results:
Significantly higher erythropoietin was found at baseline in children with CP compared with the comparison group. There was a strong response to lipopolysaccharide for interleukin-8, VEGF, TNF-α, and GM-CSF in both children with CP and the comparison group; however, there was significant lipopolysaccharide hyporesponsiveness in children with CP compared with the comparison group for interleukin-1α, interleukin-1β, interleukin-2, and interleukin-6.
Interpretation:
Altered cytokine responses in children with CP compared with the comparison group demonstrate an altered inflammatory state that may contribute to ongoing sequelae and could be a target for therapy.
What This Paper Adds:
Altered inflammatory responses persist in children with cerebral palsy (CP). Erythropoietin is elevated in children with CP compared with the comparison group. Children with CP have reduced interleukin-1α, interleukin-1β, interleukin-2, and interleukin-6 inflammatory responses to lipopolysaccharide.
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