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Cited by 98Down syndrome and intellectual disability researchAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Aberrations in circulating inflammatory cytokine levels in patients with Down syndrome: a meta-analysis

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Zhang, Yan, Che, Meng, Yuan, Jing, Yu, Yun, Cao, Chang, Qin, Xiao-Yan, Cheng, Yong·2017·Oncotarget
DOI 10.18632/oncotarget.21060PMC PMC5663613
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Abstract

// Yan Zhang 1 , Meng Che 1 , Jing Yuan 1 , Yun Yu 1 , Chang Cao 1 , Xiao-Yan Qin 1 and Yong Cheng 1 1 Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China Correspondence to: Yong Cheng, email: yongcheng@muc.edu.cn Keywords: cytokine, inflammation, Down syndrome, meta-analysis, systematic review Received: July 26, 2017 Accepted: September 03, 2017 Published: September 19, 2017 ABSTRACT Evidence suggests that immune system alterations in Down syndrome (DS) may be early events that drive neuropathological and cognitive changes of Alzheimer’s disease. The primary objective of this meta-analysis was to investigate whether there is an abnormal cytokine profile in DS patients when compared with healthy control (HC) subjects. A systematic search of Pubmed and Web of Science identified 19 studies with 957 DS patients and 541 HC subjects for this meta-analysis. Random effects meta-analysis demonstrated that patients with DS had significantly increased circulating tumor necrosis factor-α (Hedges’ g = 1.045, 95% confidence interval (CI) = 0.192 to 1.898, p = 0.016), interleukin (IL)-1β (Hedges’ g = 0.696, 95% confidence CI = 0.149 to 1.242, p = 0.013), interferon-γ (Hedges’ g = 0.978, 95% CI = 0.417 to 1.539, p = 0.001) and neopterin (Hedges’ g = 0.815, 95% CI = 0.423 to 1.207, p < 0.001) levels compared to HC subjects. No significant differences were found between patients with DS and controls for concentrations of IL-4, IL-6, IL8 and IL-10. In addition, most of the cytokine data in this meta-analysis were from children with DS and HC, and subgroup analysis showed that children with DS had elevated tumor necrosis factor-α, IL-1β and interferon-γ levels when compared with controls. Taken together, these results demonstrated that patients (children) with DS are accompanied by increased circulating cytokine tumor necrosis factor-α, IL-1β and interferon-γ levels, strengthening the clinical evidence that patients (children) with DS are accompanied by an abnormal inflammatory response.

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  • Both individuals with DS and mouse models of DS experience constitutive hyperactivation of interferon (IFN) signaling with signs of chronic inflammation and immune dysregulation, which could exacerbate the neuroinflammatory response.

    “Notably, both individuals with DS and mouse models of DS experience constitutive hyperactivation of interferon (IFN) signaling with signs of chronic inflammation and immune dysregulation,30,31,32,33,34,35,36,37,38,39,40 that could exacerbate the neuroinflammatory response.”

    From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [30]

    The Discussion reports elevated IFN-γ and neopterin in patients with Down syndrome and describes this as evidence of IFN-γ pathway hyperactivity and a heightened inflammatory response. It does not study mouse models or establish constitutive hyperactivation of IFN signaling in them. It suggests that IFN signaling may accelerate AD neuropathogenesis in Down syndrome, rather than demonstrating an exacerbated neuroinflammatory response. (LLM, conf=0.86)

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  • People with DS present increased IFN signaling likely driven by triplication of four of the six IFN receptors encoded on HSA21, rather than by massive elevation of IFN ligands, and this has been associated with chronic immune dysregulation.

    “people with DS present an increased IFN signaling likely driven by triplication of four of the six IFN receptors encoded on HSA21,36 rather than by massive elevation of the IFN ligands themselves as seen in interferonopathies,80 and this has been associated with chronic immune dysregulation.”

    From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [30]

    The Discussion reports hyperactivity of the IFN-γ pathway and an aberrant inflammatory response in people with Down syndrome. The Results and Discussion also report significantly elevated circulating IFN-γ, with a large effect size. The paper does not compare ligand levels with interferonopathies or establish that ligand elevation is not massive; the receptor-triplication detail is attached to a different citation in the citing sentence. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Zhang, Y., Che, M., Yuan, J., Yu, Y., Cao, C., Qin, X.-Y., & Cheng, Y.
Affiliations
Minzu University of China (CN)
Corresponding author
Cheng, Yong
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2017-09-19
Volume
8
Issue
48
Pages
84489-84496
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.21060
PMC
PMC5663613
OpenAlex
W2756004609
Cited by
98
References
3
Citations by year
2026: 11 · 2025: 9 · 2024: 17 · 2023: 9 · 2022: 8 · 2021: 16 · 2020: 16 · 2019: 10 · 2018: 2
FWCI
1.24
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Higher Education Discipline Innovation Project
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Down syndrome, serum cytokines, inflammatory cytokines, TNF-α, IL-1β, interferon-gamma, neopterin, immune system alterations, children, Alzheimer's disease risk, neuroinflammation, cognitive impairment, IL-4, interleukin-6, interleukin-8, IL-10, subgroup analysis by age and sex

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