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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.
Cytokine 2014; 69(2):248-54C

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.

Authors+Show Affiliations

ER030-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. Electronic address: jose.noel.ibrahim@univ-poitiers.fr.ER030-EDST, Faculty of Sciences II, Lebanese University, Fanar, BP 90656 Jdeidet El Metn, Lebanon. Electronic address: rjounblat@ul.edu.lb.Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC), EA4331, University and Hospital of Poitiers, 86022 Poitiers, France. Electronic address: adriana.delwail@univ-poitiers.fr.Medical Genetics Unit, Faculty of Medicine, Saint Joseph University, BP 17-5208 Mar Mikhael, Beirut 1104 2020, Lebanon. Electronic address: joelle.aboughoch@usj.edu.lb.Medical Genetics Unit, Faculty of Medicine, Saint Joseph University, BP 17-5208 Mar Mikhael, Beirut 1104 2020, Lebanon. Electronic address: nabiha.salem@usj.edu.lb.Medical Genetics Unit, Faculty of Medicine, Saint Joseph University, BP 17-5208 Mar Mikhael, Beirut 1104 2020, Lebanon. Electronic address: eliane.chouery@usj.edu.lb.Medical Genetics Unit, Faculty of Medicine, Saint Joseph University, BP 17-5208 Mar Mikhael, Beirut 1104 2020, Lebanon. Electronic address: megarbane@usj.edu.lb.ER030-EDST, Faculty of Sciences II, Lebanese University, Fanar, BP 90656 Jdeidet El Metn, Lebanon. Electronic address: myrnahachem@ul.edu.lb.Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC), EA4331, University and Hospital of Poitiers, 86022 Poitiers, France. Electronic address: jean-claude.lecron@univ-poitiers.fr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25025954

Citation

Ibrahim, José-Noel, et al. "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." Cytokine, vol. 69, no. 2, 2014, pp. 248-54.
Ibrahim JN, Jounblat R, Delwail A, et al. 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. Cytokine. 2014;69(2):248-54.
Ibrahim, J. N., Jounblat, R., Delwail, A., Abou-Ghoch, J., Salem, N., Chouery, E., ... Lecron, J. C. (2014). 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. Cytokine, 69(2), pp. 248-54. doi:10.1016/j.cyto.2014.06.012.
Ibrahim JN, et al. 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. Cytokine. 2014;69(2):248-54. PubMed PMID: 25025954.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Ibrahim,José-Noel, AU - Jounblat,Rania, AU - Delwail,Adriana, AU - Abou-Ghoch,Joelle, AU - Salem,Nabiha, AU - Chouery,Eliane, AU - Megarbane,André, AU - Medlej-Hashim,Myrna, AU - Lecron,Jean-Claude, Y1 - 2014/07/12/ PY - 2014/03/22/received PY - 2014/05/26/revised PY - 2014/06/08/accepted PY - 2014/7/16/entrez PY - 2014/7/16/pubmed PY - 2015/9/12/medline KW - Cytokine KW - Ex vivo KW - FMF KW - Inflammasome KW - PBMC SP - 248 EP - 54 JF - Cytokine JO - Cytokine VL - 69 IS - 2 N2 - 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. SN - 1096-0023 UR - https://www.unboundmedicine.com/medline/citation/25025954/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-4666(14)00172-0 DB - PRIME DP - Unbound Medicine ER -