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Cytokine Signature in Schnitzler Syndrome: Proinflammatory Cytokine Production Associated to Th Suppression
- Source :
- Frontiers in Immunology, Frontiers in Immunology, Vol 11 (2020)
- Publication Year :
- 2020
- Publisher :
- Frontiers Media S.A., 2020.
-
Abstract
- BackgroundSchnitzler 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.ObjectiveTo determine ex vivo cytokine profiles of Peripheral Blood Mononuclear Cells (PBMCs) from SchS patients prior to treatment and after initiation of anti-IL-1 therapy (anakinra). The sera cytokine profile was studied in parallel.MethodsWe 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.ResultsSpontaneous 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 (p = 0.04).ConclusionOur 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.
- Subjects :
- lcsh:Immunologic diseases. Allergy
0301 basic medicine
Adult
Lipopolysaccharides
Male
PBMC (peripheral blood mononuclear cells)
medicine.medical_treatment
Immunology
Inflammation
Peripheral blood mononuclear cell
Proinflammatory cytokine
03 medical and health sciences
0302 clinical medicine
Schnitzler syndrome
inflammasome
Gammopathy
medicine
Immunology and Allergy
Humans
Cells, Cultured
Original Research
Aged
Aged, 80 and over
business.industry
IL-1
IL-1 antagonist
Interleukin
T-Lymphocytes, Helper-Inducer
Middle Aged
medicine.disease
cytokines
Interleukin 1 Receptor Antagonist Protein
030104 developmental biology
Cytokine
030228 respiratory system
Antirheumatic Agents
ex vivo
Tumor necrosis factor alpha
Female
medicine.symptom
lcsh:RC581-607
business
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....d1bf8db0a701bb7d4c3700a84fa211ed