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Tigran K. Davtyan

Tigran K. Davtyan

Scientific Centre of Drug and Medical Technology Expertise, Republic of Armenia

Title: Impaired resolution of inflammation and endotoxin tolerance induction in auto inflammation

Biography

Tigran K. Davtyan is currently working in the Analytical laboratory branch, Scientific Centre of Drug and Medical Technology Expertise Ministry of Health Republic of Armenia.The mission of the Scientific Centre of Drug and Medical Technology Expertise is to implement the national drug policy, to ensure the safety, efficacy and quality of medicinal products.

Abstract

Purpose: Th e nature of 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 infl ammatory threshold we studied the IL-10 production by monocytes and dendritic cells and endotoxin tolerance induction in FMF patients. Methods: 46 attack free FMF patients included in this study. Th e production of IL-10 by NLR- or TLR-agonists stimulated monocytes and dendritic cells assayed either by conventional ELISA and fl ow cytometry. Versatility of monocytes studied by measuring the production of IL-10 and IL-1β aft er stimulation by pro- and anti-infl ammatory agents, and aft er stimulation arrest or a further counter stimulation. Monocyte endotoxin tolerance and cross-tolerance induction assayed by measuring the production of IL-1β, IL-10, TNF-α and IFN-γ aft er pre-stimulation by NLR- or TLR-ligands and aft er 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. Th e production of IL-10 by TLR- and NLR-agonists stimulated monocytes and dendritic cells is declined in FMF patients. Monocytes isolated from FMF patients failed to switch from a pro-infl ammatory activated state to antiinfl ammatory phenotype and still produce IL-1β but not IL-10, which cause impaired endotoxin tolerance and cross-tolerance induction. Th e IL-10 production and endotoxin tolerance induction by monocytes and dendritic cells restored by NOD2- ligand MDP and colchicine treatment. Conclusion: Reduced IL-10 production associated with impaired setting of feedback inhibition of infl ammatory response and caused impaired resolution of infl ammation and endotoxin tolerance induction.

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