Ex vivo PBMC cytokine profile in familial Mediterranean fever patients: Involvement of IL-1β, IL-1α and Th17-associated cytokines and decrease of Th1 and Th2 cytokines.

[familial mediterranean fever]

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 24 h stimulation of monocytes by LPS and T lymphocytes by anti-CD 3 /CD 28 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 -1 β and IL -1 α 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-CD 3 /CD 28 stimulated PBMCs supernatants of patients during crises compared to remission and controls . The Th 17 cytokines IL -17 and IL -22 were respectively higher in anti-CD 3 /CD 28 stimulated PBMC supernatants of FMF patients during and between crises compared to controls . Amongst cytokines tested in serum , only IL -6 and TNF α 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 M 694 V homozygous patients . The absence of spontaneous IL -1 β release by PBMCs reflects no constitutive activation of the inflammasome in FMF physiopathology .