Cytokine dysregulation in children with severe neurological impairment correlates with significant clinical outcomes
BackgroundChildren with neurological disorders have altered inflammatory responses. We aimed to describe pro-inflammatory, anti-inflammatory and hypoxia-induced cytokines in serum, at baseline, and in response to stimulation of whole blood with lipopolysaccharide, in children with Severe Neurologica...
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Frontiers Media S.A.
2025-06-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2025.1567221/full |
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| author | John Allen John Allen John Allen John Allen Johana Isaza-Correa Johana Isaza-Correa Johana Isaza-Correa Lynne Kelly Lynne Kelly Lynne Kelly Ashanty Melo Ashanty Melo Ashanty Melo Conor Power Conor Power Conor Power Aoife Mahony Aoife Mahony Aoife Mahony Denise McDonald Denise McDonald Denise McDonald Denise McDonald Eleanor J. Molloy Eleanor J. Molloy Eleanor J. Molloy Eleanor J. Molloy Eleanor J. Molloy Eleanor J. Molloy |
| author_facet | John Allen John Allen John Allen John Allen Johana Isaza-Correa Johana Isaza-Correa Johana Isaza-Correa Lynne Kelly Lynne Kelly Lynne Kelly Ashanty Melo Ashanty Melo Ashanty Melo Conor Power Conor Power Conor Power Aoife Mahony Aoife Mahony Aoife Mahony Denise McDonald Denise McDonald Denise McDonald Denise McDonald Eleanor J. Molloy Eleanor J. Molloy Eleanor J. Molloy Eleanor J. Molloy Eleanor J. Molloy Eleanor J. Molloy |
| author_sort | John Allen |
| collection | DOAJ |
| description | BackgroundChildren with neurological disorders have altered inflammatory responses. We aimed to describe pro-inflammatory, anti-inflammatory and hypoxia-induced cytokines in serum, at baseline, and in response to stimulation of whole blood with lipopolysaccharide, in children with Severe Neurological Impairment (SNI) compared to controls.MethodsWhole blood samples from children with SNI and healthy controls were incubated in the presence or absence of lipopolysaccharide (LPS). Serum was isolated and 12 cytokines were analysed by ELISA. Select clinical data was collected from healthcare records and correlated with cytokine results.ResultsTwenty-nine children with SNI (n = 14) and age-matched controls (n = 15) were recruited. Cytokine responses to lipopolysaccharide were similar between the groups for Interferon (INF)-γ, Interleukin(IL)-18, Tumour Necrosis Factor(TNF)-β, IL-10, IL-1ra, IL-1β, IL-8, TNF-α and Vascular Endothelial Growth Factor (VEGF). Granulocyte Monocyte Colony Stimulating Factor (GM-CSF) increased in response to LPS in the control group (p = 0.04) but not in those with SNI (p = 0.07). The SNI cohort had a significantly greater increase in EPO in response to LPS than controls (p = 0.006). IL-6 in the SNI cohort was relatively hyporesponsive to LPS (p = 0.01). Correlations were found in LPS responses as follows: number of antiseizure medications and IL-1ra (p = 0.01) and TNF-α (p = 0.04); number of infections within the last year and IL-18 (p = 0.02); requirement for enteral feeding and IL-10 (p = 0.03) and EPO (p = 0.001); use of prophylactic antibiotics and IL-10 (p = 0.001); requirement for respiratory support and VEGF (p = 0.007).ConclusionChildren with SNI have persistent altered inflammatory responses. These alterations may contribute to tertiary neurological injury and impaired ability to respond to infection and may provide a target for immunomodulation. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-2d8506aac40e43a3b0810e656427d33d2025-08-20T03:29:48ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602025-06-011310.3389/fped.2025.15672211567221Cytokine dysregulation in children with severe neurological impairment correlates with significant clinical outcomesJohn Allen0John Allen1John Allen2John Allen3Johana Isaza-Correa4Johana Isaza-Correa5Johana Isaza-Correa6Lynne Kelly7Lynne Kelly8Lynne Kelly9Ashanty Melo10Ashanty Melo11Ashanty Melo12Conor Power13Conor Power14Conor Power15Aoife Mahony16Aoife Mahony17Aoife Mahony18Denise McDonald19Denise McDonald20Denise McDonald21Denise McDonald22Eleanor J. Molloy23Eleanor J. Molloy24Eleanor J. Molloy25Eleanor J. Molloy26Eleanor J. Molloy27Eleanor J. Molloy28Discipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, IrelandTrinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, IrelandTrinity Translational Medicine Institute (TTMI), St James Hospital, Dublin, IrelandPalliative Care, Children's Health Ireland (CHI), Dublin, IrelandDiscipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, IrelandTrinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, IrelandTrinity Translational Medicine Institute (TTMI), St James Hospital, Dublin, IrelandDiscipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, IrelandTrinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, IrelandTrinity Translational Medicine Institute (TTMI), St James Hospital, Dublin, IrelandDiscipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, IrelandTrinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, IrelandTrinity Translational Medicine Institute (TTMI), St James Hospital, Dublin, IrelandDiscipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, IrelandTrinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, IrelandTrinity Translational Medicine Institute (TTMI), St James Hospital, Dublin, IrelandDiscipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, IrelandTrinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, IrelandNeurodisability, Children's Health Ireland (CHI), Dublin, IrelandDiscipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, IrelandTrinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, IrelandTrinity Translational Medicine Institute (TTMI), St James Hospital, Dublin, IrelandNeurodisability, Children's Health Ireland (CHI), Dublin, IrelandDiscipline of Paediatrics, Trinity College Dublin, The University of Dublin, Dublin, IrelandTrinity Research in Childhood Centre (TRiCC), Trinity College Dublin, Dublin, IrelandTrinity Translational Medicine Institute (TTMI), St James Hospital, Dublin, IrelandNeurodisability, Children's Health Ireland (CHI), Dublin, IrelandNeonatology, Children's Health Ireland (CHI), Dublin, IrelandPaediatrics, Coombe Hospital, Dublin, IrelandBackgroundChildren with neurological disorders have altered inflammatory responses. We aimed to describe pro-inflammatory, anti-inflammatory and hypoxia-induced cytokines in serum, at baseline, and in response to stimulation of whole blood with lipopolysaccharide, in children with Severe Neurological Impairment (SNI) compared to controls.MethodsWhole blood samples from children with SNI and healthy controls were incubated in the presence or absence of lipopolysaccharide (LPS). Serum was isolated and 12 cytokines were analysed by ELISA. Select clinical data was collected from healthcare records and correlated with cytokine results.ResultsTwenty-nine children with SNI (n = 14) and age-matched controls (n = 15) were recruited. Cytokine responses to lipopolysaccharide were similar between the groups for Interferon (INF)-γ, Interleukin(IL)-18, Tumour Necrosis Factor(TNF)-β, IL-10, IL-1ra, IL-1β, IL-8, TNF-α and Vascular Endothelial Growth Factor (VEGF). Granulocyte Monocyte Colony Stimulating Factor (GM-CSF) increased in response to LPS in the control group (p = 0.04) but not in those with SNI (p = 0.07). The SNI cohort had a significantly greater increase in EPO in response to LPS than controls (p = 0.006). IL-6 in the SNI cohort was relatively hyporesponsive to LPS (p = 0.01). Correlations were found in LPS responses as follows: number of antiseizure medications and IL-1ra (p = 0.01) and TNF-α (p = 0.04); number of infections within the last year and IL-18 (p = 0.02); requirement for enteral feeding and IL-10 (p = 0.03) and EPO (p = 0.001); use of prophylactic antibiotics and IL-10 (p = 0.001); requirement for respiratory support and VEGF (p = 0.007).ConclusionChildren with SNI have persistent altered inflammatory responses. These alterations may contribute to tertiary neurological injury and impaired ability to respond to infection and may provide a target for immunomodulation.https://www.frontiersin.org/articles/10.3389/fped.2025.1567221/fullcytokinesevere neurological impairmentinflammationlipopolysaccharideELISA |
| spellingShingle | John Allen John Allen John Allen John Allen Johana Isaza-Correa Johana Isaza-Correa Johana Isaza-Correa Lynne Kelly Lynne Kelly Lynne Kelly Ashanty Melo Ashanty Melo Ashanty Melo Conor Power Conor Power Conor Power Aoife Mahony Aoife Mahony Aoife Mahony Denise McDonald Denise McDonald Denise McDonald Denise McDonald Eleanor J. Molloy Eleanor J. Molloy Eleanor J. Molloy Eleanor J. Molloy Eleanor J. Molloy Eleanor J. Molloy Cytokine dysregulation in children with severe neurological impairment correlates with significant clinical outcomes Frontiers in Pediatrics cytokine severe neurological impairment inflammation lipopolysaccharide ELISA |
| title | Cytokine dysregulation in children with severe neurological impairment correlates with significant clinical outcomes |
| title_full | Cytokine dysregulation in children with severe neurological impairment correlates with significant clinical outcomes |
| title_fullStr | Cytokine dysregulation in children with severe neurological impairment correlates with significant clinical outcomes |
| title_full_unstemmed | Cytokine dysregulation in children with severe neurological impairment correlates with significant clinical outcomes |
| title_short | Cytokine dysregulation in children with severe neurological impairment correlates with significant clinical outcomes |
| title_sort | cytokine dysregulation in children with severe neurological impairment correlates with significant clinical outcomes |
| topic | cytokine severe neurological impairment inflammation lipopolysaccharide ELISA |
| url | https://www.frontiersin.org/articles/10.3389/fped.2025.1567221/full |
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