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Increased systemic inflammation in children with Down syndrome

Dean Huggard1, Lynne Kelly2, Emer Ryan2

  • 1Paediatrics, 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.

Cytokine
|December 1, 2019
PubMed

Insights

Children with Down syndrome (DS) show higher levels of inflammatory and anti-inflammatory cytokines, impacting infection and autoimmunity risks. These cytokine differences may explain varied clinical outcomes in DS patients.

Area of Science:

  • Immunology
  • Genetics
  • Pediatrics

Background:

  • Children with Down syndrome (DS) experience increased infections, sepsis mortality, and chronic inflammatory conditions.
  • Cytokine dysregulation is implicated in DS clinical sequelae, with elevated pro-inflammatory biomarkers noted in adults.
  • The roles of anti-inflammatory mediators (IL-1ra, IL-10) and cytokines (Epo, VEGF) in DS, particularly concerning congenital heart disease (CHD), are not fully understood.

Purpose of the Study:

  • To comprehensively examine pro-inflammatory (IL-2, IL-6, IL-8, IL-18, IL-1β, TNF-α, IFN-γ) and anti-inflammatory (IL-10, IL-1ra) mediators in children with DS.
  • To investigate the influence of hypoxia-related (EPO), angiogenesis-related (VEGF), and myelopoiesis-related (GM-CSF) cytokines.
  • To discuss the impact of congenital heart disease (CHD) and lipopolysaccharide (LPS) on these mediators.

Main Methods:

  • Enzyme-linked immunosorbent assay (ELISA) was used to quantify a wide range of cytokines.
  • 114 children with Down syndrome and 60 age/sex-matched controls were recruited.
  • Analysis included baseline cytokine levels and responses to LPS stimulation.

Main Results:

  • Children with Down syndrome exhibited significantly higher baseline levels of pro-inflammatory cytokines (IL-2, IL-6), anti-inflammatory cytokines (IL-10, IL-1ra), and other mediators (Epo, VEGF, GM-CSF).
  • Congenital heart disease (CHD) did not appear to significantly alter circulating cytokine levels outside the acute surgical phase.
  • Both Down syndrome and control groups showed similar responses when stimulated with LPS.

Conclusions:

  • Elevated pro- and anti-inflammatory cytokine profiles in children with Down syndrome may contribute to their increased susceptibility to infections and autoimmune conditions.
  • These distinct cytokine patterns could underlie the varied clinical outcomes observed in Down syndrome.
  • Further research into these cytokine differences is warranted to understand and potentially mitigate clinical sequelae in DS.

Keywords:
CytokinesDown syndromeInflammationInnate immunity

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