IL-33 and its decoy sST2 in patients with Alzheimer's disease and mild cognitive impairment.
Alzheimer’s disease
Inflammation
Interleukin 33
sST2 decoy receptor
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
06 Jun 2020
06 Jun 2020
Historique:
received:
18
11
2019
accepted:
06
04
2020
entrez:
8
6
2020
pubmed:
9
6
2020
medline:
1
4
2021
Statut:
epublish
Résumé
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). 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 Aβ 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 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.
Sections du résumé
BACKGROUND
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
METHODS
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 Aβ
RESULTS
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
CONCLUSIONS
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.
Identifiants
pubmed: 32505187
doi: 10.1186/s12974-020-01806-4
pii: 10.1186/s12974-020-01806-4
pmc: PMC7276088
doi:
Substances chimiques
Biomarkers
0
IL1RL1 protein, human
0
IL33 protein, human
0
Interleukin-1 Receptor-Like 1 Protein
0
Interleukin-33
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
174Références
Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):E1316-25
pubmed: 26884167
Mol Neurodegener. 2016 Mar 03;11:23
pubmed: 26939933
Proc Natl Acad Sci U S A. 2016 May 10;113(19):E2705-13
pubmed: 27091974
Nat Immunol. 2004 Apr;5(4):373-9
pubmed: 15004556
Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1673-8
pubmed: 22307629
J Alzheimers Dis. 2018;66(3):1131-1144
pubmed: 30400090
Brain Behav Immun. 2015 Feb;44:68-81
pubmed: 25153903
J Immunol. 2007 Aug 15;179(4):2551-5
pubmed: 17675517
Immunity. 2014 Mar 20;40(3):425-35
pubmed: 24613091
J Psychiatr Res. 1975 Nov;12(3):189-98
pubmed: 1202204
Immunity. 2015 Jul 21;43(1):161-74
pubmed: 26092469
Nat Immunol. 2016 Feb;17(2):122-31
pubmed: 26784265
J Immunol. 2010 May 15;184(10):5802-8
pubmed: 20400705
Neurobiol Aging. 2004 Sep;25(8):1009-15
pubmed: 15212825
PLoS Pathog. 2017 Apr 27;13(4):e1006322
pubmed: 28448579
J Alzheimers Dis. 2014;38(2):403-13
pubmed: 23979026
Immunity. 2009 Jul 17;31(1):84-98
pubmed: 19559631
Brain Behav Immun. 2011 Mar;25(3):539-47
pubmed: 21167930
Sci Rep. 2017 Dec 1;7(1):16760
pubmed: 29196629
Neuroscience. 2018 Jan 15;369:222-230
pubmed: 29175156
J Immunol. 2009 Nov 15;183(10):6469-77
pubmed: 19841166
PLoS One. 2012;7(9):e45225
pubmed: 23028861
Arch Neurol. 1999 Mar;56(3):303-8
pubmed: 10190820
Nature. 2013 Jan 31;493(7434):674-8
pubmed: 23254930
Mech Ageing Dev. 1984 Nov;28(1):47-55
pubmed: 6513613
J Clin Invest. 2007 Jun;117(6):1538-49
pubmed: 17492053
Immunity. 2012 Mar 23;36(3):451-63
pubmed: 22425247
Neurobiol Aging. 2012 Mar;33(3):624.e11-22
pubmed: 21514692
Exp Mol Med. 2017 Nov 3;49(11):e388
pubmed: 29099095
J Alzheimers Dis. 2016 Mar 16;52(2):483-95
pubmed: 27003214
Nat Immunol. 2008 Aug;9(8):857-65
pubmed: 18604209
Nat Commun. 2017 Apr 04;8:14919
pubmed: 28374774
J Immunol. 2011 Aug 15;187(4):1609-16
pubmed: 21734074
Eur J Immunol. 2011 Jun;41(6):1675-86
pubmed: 21469105
Br J Psychiatry. 1982 Jun;140:566-72
pubmed: 7104545
Lancet Neurol. 2014 Jun;13(6):614-29
pubmed: 24849862
Eur J Immunol. 2012 Jul;42(7):1804-14
pubmed: 22585447
Brain. 2016 Apr;139(Pt 4):1237-51
pubmed: 26912648
Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15502-7
pubmed: 25313073
Int Immunol. 2008 Jun;20(6):791-800
pubmed: 18448455
J Alzheimers Dis. 2014;40(2):297-308
pubmed: 24413615
Mol Psychiatry. 2009 Nov;14(11):1004-16
pubmed: 19204726
Front Aging Neurosci. 2013 Nov 25;5:81
pubmed: 24324435
Alzheimers Dement. 2011 May;7(3):263-9
pubmed: 21514250
Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):9021-6
pubmed: 19439663
Immunity. 2005 Nov;23(5):479-90
pubmed: 16286016
Trends Immunol. 2016 May;37(5):321-333
pubmed: 27055914
Nature. 2014 Sep 25;513(7519):564-568
pubmed: 25043027
J Alzheimers Dis. 2010;21(3):927-38
pubmed: 20634592