Toll-like receptor 4-mediated cytokine synthesis and post-stroke depressive symptoms.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
26 04 2021
26 04 2021
Historique:
received:
29
12
2020
accepted:
09
04
2021
revised:
27
03
2021
entrez:
27
4
2021
pubmed:
28
4
2021
medline:
29
6
2021
Statut:
epublish
Résumé
Altered cytokine synthesis thought to contribute to the pathophysiology of post-stroke depression (PSD). Toll-like receptor 4 (TLR4) is a master regulator of innate immunity. The aim of this study was to explore the putative association between TLR4-mediated cytokine synthesis and subsequent symptoms of PSD. In total, 262 patients with ischemic stroke and without a history of PSD were included. Depressive symptoms were assessed using the Patient Health Questionnaire-9 in 170 patients on Day 8 and in 146 at 3 months after stroke. Blood samples taken on Day 3 after stroke were stimulated ex vivo with lipopolysaccharide (LPS). Ex vivo synthesized cytokines (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12p70) and circulating cytokines (TNFα, IL-6, sIL-6R, and IL-1ra) were measured using the enzyme-linked immunoassay or cytometric method. RNA sequencing was used to determine the gene expression profile of LPS-induced cytokines and chemokines. LPS-induced cytokine synthesis and the gene expression of TLR4-dependent cytokines and chemokines did not differ between patients with and without greater depressive symptoms. The plasma level of IL-6, but not TNFα, sIL-6R, and IL-1ra, was higher in patients who developed depressive symptoms at 3 months after stroke (median: 4.7 vs 3.4 pg/mL, P = 0.06). Plasma IL-6 predicted the severity of depressive symptoms at 3 months after stroke (β = 0.42, P = 0.03). In conclusion, TLR4-dependent cytokine synthesis was not associated with greater post-stroke depressive symptoms in this study. Circulating IL-6 might be associated with depressive symptoms occurring at 3 months after stroke.
Identifiants
pubmed: 33903586
doi: 10.1038/s41398-021-01359-x
pii: 10.1038/s41398-021-01359-x
pmc: PMC8076201
doi:
Substances chimiques
Cytokines
0
Lipopolysaccharides
0
TLR4 protein, human
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
246Subventions
Organisme : Narodowe Centrum Nauki (National Science Centre)
ID : 2015/19/B/NZ4/00287
Références
BMJ. 2019 Apr 9;365:l1476
pubmed: 30967483
Neurol Res. 2010 May;32(4):340-6
pubmed: 20482998
Brain Res. 2020 Jun 1;1736:146777
pubmed: 32171705
Mol Psychiatry. 2006 Nov;11(11):984-91
pubmed: 16894392
Blood. 2000 Oct 1;96(7):2584-91
pubmed: 11001915
Nat Rev Immunol. 2016 Jan;16(1):22-34
pubmed: 26711676
Arch Gen Psychiatry. 2001 May;58(5):445-52
pubmed: 11343523
Biol Psychiatry. 2009 Sep 1;66(5):407-14
pubmed: 19423079
Br J Psychiatry. 2013 Jan;202(1):14-21
pubmed: 23284148
Exp Gerontol. 2007 Jul;42(7):693-701
pubmed: 17350781
Int Immunol. 2005 Jan;17(1):1-14
pubmed: 15585605
Br J Psychiatry. 1988 Feb;152:209-13
pubmed: 3167337
J Neuroinflammation. 2020 Jan 6;17(1):7
pubmed: 31906994
Int J Stroke. 2014 Dec;9(8):1017-25
pubmed: 25117911
Nature. 2005 Oct 13;437(7061):1032-7
pubmed: 16136080
Exp Ther Med. 2016 Sep;12(3):1591-1598
pubmed: 27588080
J Cereb Blood Flow Metab. 2008 Sep;28(9):1588-96
pubmed: 18523439
Brain Behav Immun. 2015 Oct;49:206-15
pubmed: 26065825
Biol Pharm Bull. 2006 Dec;29(12):2399-403
pubmed: 17142971
Front Neurol. 2017 Sep 21;8:498
pubmed: 28983281
Expert Opin Ther Targets. 2019 Oct;23(10):865-882
pubmed: 31580163
BMC Neurol. 2007 Feb 28;7:5
pubmed: 17328808
Psychol Med. 2015 Jan;45(1):29-49
pubmed: 25066635
Psychoneuroendocrinology. 2020 Nov;121:104843
pubmed: 32911436
J Affect Disord. 2015 Jul 1;179:88-94
pubmed: 25855618
Mol Psychiatry. 2016 Dec;21(12):1696-1709
pubmed: 26903267
Biol Psychiatry. 2009 May 1;65(9):732-41
pubmed: 19150053
Neuropsychiatr Dis Treat. 2014 Sep 22;10:1827-35
pubmed: 25285006
Stroke. 1994 Nov;25(11):2220-6
pubmed: 7974549
J Neuropsychiatry Clin Neurosci. 2013 Fall;25(4):255-63
pubmed: 24247852
Mol Psychiatry. 2014 Dec;19(12):1267-74
pubmed: 24296977
Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):16136-41
pubmed: 25331895
JAMA Psychiatry. 2014 Oct;71(10):1121-8
pubmed: 25133871
Nurs Res. 2012 Sep-Oct;61(5):333-41
pubmed: 22710475
Neurobiol Stress. 2016 Mar 29;4:15-22
pubmed: 27981186
Psychol Med. 2009 Jul;39(7):1201-9
pubmed: 19356259
Gen Hosp Psychiatry. 2012 Jan-Feb;34(1):35-9
pubmed: 22055333
Psychoneuroendocrinology. 2016 Oct;72:156-60
pubmed: 27428088
J Immunol. 2001 Nov 15;167(10):5887-94
pubmed: 11698465
Biol Psychiatry. 2010 Mar 1;67(5):446-57
pubmed: 20015486
Stroke. 2005 Mar;36(3):635-8
pubmed: 15677576
Expert Rev Neurother. 2015 May;15(5):523-31
pubmed: 25865856
Psychopharmacology (Berl). 2016 May;233(9):1707-14
pubmed: 26415953
Biol Psychiatry. 2010 Jul 15;68(2):179-86
pubmed: 20471630
Transl Psychiatry. 2016 May 31;6(5):e825
pubmed: 27244234
Stroke. 1993 Jan;24(1):35-41
pubmed: 7678184
Neural Regen Res. 2015 Sep;10(9):1349-55
pubmed: 26604877
Depress Anxiety. 2013 Apr;30(4):297-306
pubmed: 23468190
Stroke. 2009 Oct;40(10):3226-32
pubmed: 19661470
Mol Psychiatry. 2018 Feb;23(2):335-343
pubmed: 27752078
J Gen Intern Med. 2001 Sep;16(9):606-13
pubmed: 11556941
Neuropsychopharmacology. 2002 May;26(5):643-52
pubmed: 11927189
Indian J Psychiatry. 2019 May-Jun;61(3):283-289
pubmed: 31142907
Acta Psychiatr Scand. 2017 May;135(5):373-387
pubmed: 28122130
Neurobiol Dis. 2006 Sep;23(3):587-94
pubmed: 16843000
J Immunol. 2005 Aug 15;175(4):2570-8
pubmed: 16081831
Cochrane Database Syst Rev. 2016 Nov 21;11:CD011333
pubmed: 27869298