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Ex vivo PBMC cytokine profile in familial Mediterranean fever patients: Involvement of IL-1β, IL-1α and
José-Noel Ibrahim1, Rania Jounblat2, Adriana Delwail3
1ER030-EDST, Faculty of Sciences II, Lebanese University, Fanar, BP 90656 Jdeidet El Metn, Lebanon; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC), EA4331, University and Hospital of Poitiers, 86022 Poitiers, France.
Abstract:
In order to clarify the inflammatory mechanism underlying familial Mediterranean fever (FMF), we aimed to evaluate the ex vivo cytokine profile of FMF patients during acute attacks and attack-free periods, and compare it with that of healthy controls. The study included 34 FMF patients, of whom 9 were studied during attack and remission and 24 healthy controls. Cytokine levels were evaluated by Luminex technology in serum and supernatants of PBMC (Peripheral Blood Mononuclear Cells) cultures with and without 24h stimulation of monocytes by LPS and T lymphocytes by anti-CD3/CD28 beads. Levels of IL-6 and TNF-α were higher in unstimulated and LPS-stimulated PBMC supernatants of FMF patients in crises compared to controls. In response to LPS stimulation, higher levels of IL-1β and IL-1α were found in PBMC supernatants of patients during crises compared to those in remission and to controls. IFN-γ and IL-4 levels were the lowest in unstimulated and anti-CD3/CD28 stimulated PBMCs supernatants of patients during crises compared to remission and controls. The Th17 cytokines IL-17 and IL-22 were respectively higher in anti-CD3/CD28 stimulated PBMC supernatants of FMF patients during and between crises compared to controls. Amongst cytokines tested in serum, only IL-6 and TNFα were enhanced in FMF patients. The ex vivo study represents an interesting approach to evaluate cytokines' involvement in FMF. Our results suggest an ongoing subclinical inflammation and define an elevated inflammatory cytokine signature, distinctly for M694V homozygous patients. The absence of spontaneous IL-1β release by PBMCs reflects no constitutive activation of the inflammasome in FMF physiopathology.
Insights
Familial Mediterranean fever (FMF) patients exhibit elevated inflammatory cytokines during attacks, suggesting subclinical inflammation. Specific cytokine profiles were identified, particularly in M694V homozygous patients, offering insights into FMF pathogenesis.
Area of Science:
- Immunology
- Genetics
- Rheumatology
Background:
- Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder characterized by recurrent inflammatory attacks.
- Understanding the precise inflammatory mechanisms in FMF is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the ex vivo cytokine profiles of FMF patients during acute attacks and remission.
- To compare these profiles with those of healthy controls to elucidate FMF inflammatory pathways.
Main Methods:
- Serum and peripheral blood mononuclear cell (PBMC) cytokine levels were analyzed using Luminex technology in 34 FMF patients and 24 controls.
- PBMCs were stimulated with lipopolysaccharide (LPS) or anti-CD3/CD28 beads to assess cytokine responses.
Main Results:
- FMF patients showed higher levels of IL-6 and TNF-α in serum and PBMC supernatants, particularly during attacks.
- Elevated IL-1β and IL-1α were observed in LPS-stimulated PBMC supernatants during crises.
- Th17 cytokines (IL-17, IL-22) were increased in stimulated PBMC supernatants in FMF patients, irrespective of attack status.
Conclusions:
- FMF patients exhibit a distinct inflammatory cytokine signature, indicative of ongoing subclinical inflammation.
- The study highlights specific cytokine alterations associated with FMF, especially in M694V homozygous individuals.
- Results suggest no constitutive inflammasome activation in FMF, despite elevated inflammatory markers.
