IL-33 and its decoy sST2 in patients with Alzheimer’s Disease and Mild Cognitive Impairment
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-1ß 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 Aß42-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-1ß 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+Aß42-stimulated monocytes down regulated IL-1ß 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+Aß42-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.