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

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.