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Cytokine. 2019 Nov 27;127:154938. doi: 10.1016/j.cyto.2019.154938. [Epub ahead of print]

Increased systemic inflammation in children with Down syndrome.

Author information

1
Paediatrics, Trinity College, The University of Dublin, Ireland; Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Ireland; Paediatrics, Children's Hospital Ireland (CHI) at Tallaght, Tallaght University Hospital, Ireland; National Children's Research Centre, CHI at Crumlin, Dublin, Ireland. Electronic address: huggardd@tcd.ie.
2
Paediatrics, Trinity College, The University of Dublin, Ireland; Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Ireland.
3
Paediatrics, Trinity College, The University of Dublin, Ireland; Paediatrics, Children's Hospital Ireland (CHI) at Tallaght, Tallaght University Hospital, Ireland.
4
Paediatrics, Trinity College, The University of Dublin, Ireland; Immunology, CHI at Crumlin, Dublin, Ireland.
5
Paediatrics, Trinity College, The University of Dublin, Ireland; Cardiology, CHI at Crumlin, Dublin, Ireland.
6
Paediatrics, Trinity College, The University of Dublin, Ireland; Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Ireland; Paediatrics, Children's Hospital Ireland (CHI) at Tallaght, Tallaght University Hospital, Ireland; Coombe Women and Infants University Hospital, Ireland; Neonatology, CHI at Crumlin, Dublin, Ireland; National Children's Research Centre, CHI at Crumlin, Dublin, Ireland.

Abstract

Children with Down syndrome (DS) develop more infections, have an increased mortality from sepsis and an increased incidence of chronic inflammatory conditions. Cytokine dysregulation may underpin these clinical sequelae and raised pro-inflammatory biomarkers are a feature in adults with DS. The importance of the anti-inflammatory mediators IL-1ra and IL-10, as well as cytokines Epo and VEGF, which could impact on the pathogenesis and outcomes in congenital heart disease (CHD) which is more prevalent in DS, are less well known. We examined a comprehensive array of pro-(IL-2, IL-6, IL-8, IL-18, IL-1β, TNF-α, IFN-γ), and anti-inflammatory (IL-10 and IL-1ra) mediators, cytokines involved in inflammation in response to hypoxia (EPO), propagating angiogenesis (VEGF), and myelopoiesis (GM-CSF), by enzyme linked immunosorbent assay (ELISA), as well as discussing the potential impact of significant CHD and Lipopolysaccharide endotoxin on these mediators. 114 children with DS and 60 age and sex matched controls were recruited. Children with Down syndrome exhibit significantly greater levels of pro and anti-inflammatory cytokines; IL-2, IL-6, IL-10, IL-1ra, as well as increased Epo, VEGF and GM-CSF at baseline. CHD does not seem to have an impact on circulating cytokines beyond the acute surgical phase. Both cohorts had similar responses to LPS stimulation. These differences may contribute to varied clinical outcomes, acutely like in sepsis, and over time in autoimmunity.

KEYWORDS:

Cytokines; Down syndrome; Inflammation; Innate immunity

PMID:
31785499
DOI:
10.1016/j.cyto.2019.154938

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