IL-33 and its decoy sST2 in patients with Alzheimer's disease and mild cognitive impairment: Journal of Neuroinflammation

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Abstract

Background: Interleukin-33 is a cytokine endowed with pro- and anti-inflammatory properties that plays a still poorly defined role in the pathogenesis of a number of central nervous system (CNS) conditions including Alzheimer's disease (AD). We analyzed this cytokine and its decoy receptor sST2 in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Method: IL-33 and sST2 were analyzed in serum and CSF of AD and MCI patients, comparing the results to those obtained in age-matched healthy controls (HC). Because of the ambiguous role of IL-33 in inflammation, the concentration of both inflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokines was analyzed as well in serum and cerebrospinal fluid (CSF) of the same individuals. Finally, the effect of IL-33 on in vitro Aβ42-stimulated monocytes of AD, MCI, and HC individuals was examined. Results: As compared to HC, (1) IL-33 was significantly decreased in serum and CSF of AD and MCI, (2) sST2 was increased in serum of AD and MCI but was undetectable in CSF, (3) serum and CSF IL-1β concentration was significantly increased and that of IL-10 was reduced in AD and MCI, whereas no differences were observed in IL-6. In vitro addition of IL-33 to LPS+Aβ 42-stimulated monocytes downregulated IL-1β generation in MCI and HC, but not in AD, and stimulated IL-10 production in HC alone. IL-33 addition also resulted in a significant reduction of NF-kB nuclear translocation in LPS+Aβ42-stimulated monocytes of HC alone. Conclusions: These data support the hypothesis that IL-33 plays a complex anti-inflammatory role that is lost in AD- and MCI-associated neuroinflammation; results herein also suggest a possible use of IL-33 as a novel therapeutic approach in AD and MCI.

Original languageEnglish
Article number174
Pages (from-to)174
JournalJ. Neuroinflamm.
Volume17
Issue number1
DOIs
Publication statusPublished - Jun 6 2020

Keywords

  • Alzheimer's disease
  • Inflammation
  • Interleukin 33
  • sST2 decoy receptor
  • amyloid beta protein[1-42]
  • immunoglobulin enhancer binding protein
  • interleukin 1 receptor like 1 protein
  • interleukin 10
  • interleukin 1beta
  • interleukin 33
  • interleukin 6
  • soluble interleukin 1 receptor like 1 protein
  • unclassified drug
  • adult
  • aged
  • Alzheimer disease
  • Article
  • blood sampling
  • cerebrospinal fluid level
  • controlled study
  • cytokine production
  • down regulation
  • enzyme linked immunosorbent assay
  • female
  • human
  • human cell
  • male
  • mild cognitive impairment
  • Mini Mental State Examination
  • monocyte
  • neuroprotection
  • protein analysis
  • protein blood level
  • protein function
  • very elderly
  • Western blotting

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