Diminished IL-10 production is Associated with Impaired Versatility of Monocytes in Familial Mediterranean Fever
|Tigran K. Davtyan1*, Gagik S. Hakobyan2, Samvel A. Avetisyan3, Anna G. Sukiasyan4 and Yuri T. Aleksanyan4|
|1Laboratory of Immunology and Virology, "Armenicum" Research Centre, CJSC Armenicum, 37 Nalbandyan St., Yerevan, Republic of Armenia|
|2Department of Internal Medicine, Yerevan State Medical University, Koryun 2 St., Yerevan, Republic of Armenia|
|3Department of Pathophysiology; Yerevan State Medical University, Koryun 2 St., Yerevan, Republic of Armenia|
|4Laboratory of Epidemiology and Immunology, Institute of Epidemiology, Virology and Medical Parasitology, Ministry of Health RA, Yerevan, Armenia|
|Corresponding Author :||Dr. Tigran K. Davtyan, PhD, ScD
Analytical Laboratory Branch
Scientific Centre of Drug and Medical Technology Expertise JSC, Armenia
Tel: +374 10 23-72-61
Fax: +374 10 28-07-33
E-mail: [email protected]
|Received: January 15, 2014; Accepted: March 10, 2014; Published: March 17, 2014|
|Citation: Davtyan TK, Hakobyan GS, Avetisyan SA, Sukiasyan AG, Aleksanyan YT (2014) Diminished IL-10 production is Associated with Impaired Versatility of Monocytes in Familial Mediterranean Fever. J Clin Cell Immunol 5:196. doi:10.4172/2155-9899.1000196|
|Copyright: © 2014 Davtyan TK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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Purpose: The nature of the heightened endotoxin sensitivity state observed in Familial Mediterranean Fever (FMF) at present remains unknown. To assess the possibility that IL-10 plays a role in setting the inflammatory threshold, we studied IL-10 production by monocytes and dendritic cells as well as endotoxin tolerance induction in FMF patients.
Methods: 46 attack-free FMF patients were included in this study. The production of IL-10 by NLR- or TLRagonist- stimulated monocytes and dendritic cells were assayed either by conventional ELISA or flow cytometry. The versatility of monocytes was studied by measuring the production of IL-10 and IL-1β after stimulation by pro- and anti-inflammatory agents, and after stimulation arrest or a further counter stimulation. Monocyte endotoxin tolerance and cross-tolerance induction were assayed by measuring the production of IL-1β, IL-10, TNF-α and IFN-γ after prestimulation by NLR- or TLR-ligands and after re-stimulation with LPS.
Results: In FMF patients, we observed down-regulation of circulating CD36+ peripheral blood lymphoid cells but not monocytes, constitutively producing IL-10. The production of IL-10 by TLR- and NLR-agonist-stimulated monocytes and dendritic cells declines in FMF patients. Monocytes isolated from FMF patients failed to switch from a pro-inflammatory activated state to anti-inflammatory phenotype and still produce IL-1β but not IL-10, which cause impaired endotoxin tolerance and cross-tolerance induction. The IL-10 production and endotoxin tolerance induction by monocytes and dendritic cells were restored by NOD2- ligand MDP and colchicine treatment.
Conclusion: The reduced IL-10 production was associated with the impaired setting of feedback inhibition of inflammatory response and caused impaired resolution of inflammation and endotoxin tolerance induction.