Cytokine Signature in Schnitzler Syndrome: Proinflammatory Cytokine Production Associated to Th Suppression.
Adult
Aged
Aged, 80 and over
Antirheumatic Agents
/ therapeutic use
Cells, Cultured
Cytokines
/ blood
Female
Humans
Interleukin 1 Receptor Antagonist Protein
/ therapeutic use
Lipopolysaccharides
/ pharmacology
Male
Middle Aged
Schnitzler Syndrome
/ blood
T-Lymphocytes, Helper-Inducer
/ drug effects
IL-1
IL-1 antagonist
PBMC (peripheral blood mononuclear cells)
Schnitzler syndrome
cytokines
ex vivo
inflammasome
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
28
07
2020
accepted:
06
10
2020
entrez:
16
12
2020
pubmed:
17
12
2020
medline:
17
7
2021
Statut:
epublish
Résumé
Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal IgM gammopathy. Overactivation of the interleukin(IL)-1 system is reported, even though the exact pathophysiological pathways remain unknown. To determine We collected blood samples from thirty-six untreated or treated SchS. PBMCs were cultured with and without LPS or anti-CD3/CD28. Cytokine levels were evaluated in serum and cell culture supernatants using Luminex technology. Spontaneous TNFα, IL-6, IL-1β, IL-1α, and IL-1RA release by PBMCs of SchS patients were higher than in controls. LPS-stimulation further induced the secretion of these cytokines. In contrast, after T-cell stimulation, TNFα, IL-10, IFNγ, IL-17A, and IL-4 production decreased in SchS patients compared to healthy controls, but less in treated patients. Whereas IL-1β serum level was not detected in most sera, IL-6, IL-10, and TNFα serum levels were higher in patients with SchS and IFNγ and IL-4 levels were lower. Of note, IL-6 decreased after treatment in SchS ( Our data strengthen the hypothesis of myeloid inflammation in SchS, mediated in particular by IL-1β, TNFα, and IL-6, associated with overproduction of the inhibitors IL-1RA and IL-10. In contrast, we observed a loss of Th1, Th2, and Th17 cell functionalities that tends to be reversed by anakinra.
Sections du résumé
Background
Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal IgM gammopathy. Overactivation of the interleukin(IL)-1 system is reported, even though the exact pathophysiological pathways remain unknown.
Objective
To determine
Methods
We collected blood samples from thirty-six untreated or treated SchS. PBMCs were cultured with and without LPS or anti-CD3/CD28. Cytokine levels were evaluated in serum and cell culture supernatants using Luminex technology.
Results
Spontaneous TNFα, IL-6, IL-1β, IL-1α, and IL-1RA release by PBMCs of SchS patients were higher than in controls. LPS-stimulation further induced the secretion of these cytokines. In contrast, after T-cell stimulation, TNFα, IL-10, IFNγ, IL-17A, and IL-4 production decreased in SchS patients compared to healthy controls, but less in treated patients. Whereas IL-1β serum level was not detected in most sera, IL-6, IL-10, and TNFα serum levels were higher in patients with SchS and IFNγ and IL-4 levels were lower. Of note, IL-6 decreased after treatment in SchS (
Conclusion
Our data strengthen the hypothesis of myeloid inflammation in SchS, mediated in particular by IL-1β, TNFα, and IL-6, associated with overproduction of the inhibitors IL-1RA and IL-10. In contrast, we observed a loss of Th1, Th2, and Th17 cell functionalities that tends to be reversed by anakinra.
Identifiants
pubmed: 33324407
doi: 10.3389/fimmu.2020.588322
pmc: PMC7726442
doi:
Substances chimiques
Antirheumatic Agents
0
Cytokines
0
Interleukin 1 Receptor Antagonist Protein
0
Lipopolysaccharides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
588322Informations de copyright
Copyright © 2020 Masson Regnault, Frouin, Jéru, Delwail, Charreau, Barbarot, Néel, Masseau, Puéchal, Kyndt, Gayet, Lifermann, Asli, Balguerie, Blanchard-Delaunay, Aubin, Rizzi, Rongioletti, Boyé, Gusdorf, Bessis, Morel, Hainaut, Lipsker and Lecron.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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