Cytokine profile of Armenian patients with Familial Mediterranean fever

Manukyan, Gayane; Ghazaryan, Karine A.; Ktsoyan, Zh. A.; Tat'yan, M. V.; Khachatryan, Zaruhi; Hakobyan, Gagik; Mkrtchyan, V. A.; Kelly, Denise; Coutts, A. G. P.; Aminov, Rustam

doi:10.1016/j.clinbiochem.2008.03.017

Cited by 63 publications

(47 citation statements)

References 10 publications

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“…IL-6 level from cell culture supernatant of FMF patients (both spontaneous release and LPS induced production by PBMNCs) was higher than controls. Our finding is compatible with that of Aminov et al and Bagci et al who reported similar results in serum IL-6 of FMF patients (both before and during the attacks) compared to the controls 27,15 . Moreover, Notarnicola and his colleagues found that the mRNA expression of IL-6 in PBMNCs of FMF patients (in attack free period) was higher than control 28. This high level in attack free period might reflect sustained activation of the immune cells of these patients even in the resting stage.…”

Section: Discussionsupporting

confidence: 83%

Effects of different Familial Mediterranean Fever gene mutations and in vitro Colchicine treatment on Peripheral Blood Mononuclear Cells production of IL-6

Daoud

Rajab

Alawneh

et al. 2013

Bangladesh J Med Sci

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Abstract:Rationale: We wanted to study the effects of Familial Mediterranean Fever (FMF) genetic mutations in Northern Jordan population and in vitro Colchicine treatment on the peripheral blood mononuclear cells (PBMN) production of IL-6 as a marker of disease activity. Methods: -17 FMF patients and 9 controls were studied. (4 patients had exon 10 mutations only (M680I and V726A), 5 patients had exon 2 mutations (R202Q and E148Q) only and 8 patients with both exon mutations (compound homozygous or heterozygous M694V and R202Q). PBMN cells were incubated with Lipopolysaccharide at 100ng/ml or colchicine 10 ng/ml alone or both. Results: The results showed higher IL-6 levels in the FMF group than control for all treatment modalities, (108.97 vs. 56.49 ng/ml for unstimulated cells) with the highest levels when both exons are involved. Exon 10 mutations were associated with a higher IL-6 level than exon 2 mutations only. Exon 2 mutations alone also were associated with a higher than control IL-6 levels suggesting that it is not a polymorphism phenomenon and is involved in the pathogenesis. In vitro Colchicine treatment caused an increase in the production of IL-6 -although not as high as with LPS -for all groups. Conclusions: Mutations occurring in exon 10 are more significant than mutations occurring in exon 2, although both are contributing to the disease. However colchicine was associated with a paradoxical increase in IL-6 levels. This observation needs confirmation with different colchicine levels in the culture medium and warrants thinking about its exact mechanism of action.

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Section: Discussionsupporting

confidence: 83%

Effects of different Familial Mediterranean Fever gene mutations and in vitro Colchicine treatment on Peripheral Blood Mononuclear Cells production of IL-6

Daoud

Rajab

Alawneh

et al. 2013

Bangladesh J Med Sci

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“…Other studies also demonstrated that the serum IL-10 levels were not different in FMF patients with attacks and attack-free, and healthy controls [35]. In contrast, a significantly higher level of IL-10 in attack vs. control was confirmed by two independent groups of investigators [36,37]. In addition, a potentially important consideration in the analysis of human IL-10 expression is the well-described inter-individual variation in IL-10 production which is associated with single nucleotide polymorphisms in the IL-10 promoter [38,39].…”

Section: Discussionmentioning

confidence: 55%

“…However, we found that the surface expression of co-stimulatory molecules are not paralleled with the pattern of IL-10 production by differentially activated DCs and monocytes in FMF patients, further suggesting that cellular proinflammatory activation plasticity is altered in FMF and reduced the IL-10 production associated with impaired setting of feedback inhibition of the pro-inflammatory response. It has been shown that the increase of IL-10 and TGF-β1 in attack may play a compensatory and regulatory role with respect to proinflammatory cytokines and may contribute to the self-resolving nature of inflammatory attacks in FMF [36].…”

Section: Discussionmentioning

confidence: 99%

Diminished IL-10 production is Associated with Impaired Versatility of Monocytes in Familiar Mediterranean Fever

Hakobyan¹

2014

J Clin Cell Immunol

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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.

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“…In a previous study, increases in the concentrations of anti-inflammatory cytokines, IL-10 and TGF-β, were found during FMF attacks [6]. As FMF is an inflammatory disorder that is characterized mostly by proinflammatory cytokines such as IL-1, IL-6, and TNF α, the coexistence of pro and anti-inflammatory cytokines during the attacks is puzzling.…”

Section: Discussionmentioning

confidence: 95%

“…Recently, some authors have noted that on top of simple Th1 polarization, in FMF, there are also evident increases in concentrations of the anti inflammatory cytokines IL-10 and transforming growth factor (TGF)-β, both known to induce T-regs expression, suggesting a more complex picture of events [5,6]. T-regs serve to control inflammation and play an important role in autoimmune pathogenesis by maintaining self-tolerance and controlling expansion and activation of autoreactive CD4+ T effector cells [7].…”

Section: Introductionmentioning

confidence: 99%

The role of regulatory T cells in familial Mediterranean fever (FMF)

et al. 2012

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The role of regulatory T cells (T-regs) in familial Mediterranean fever (FMF) was never evaluated. Preliminary studies that we have conducted suggested a rise in the number of regulatory T cells after FMF attacks reaching a maximal level at 7 days. The aim of this study was to evaluate the percentage and activity of regulatory T cells in FMF. Six patients with refractory FMF and six healthy controls were evaluated. The percentage of T-reg cells and forkhead box protein 3 (Foxp3) expression was evaluated and compared between four states: FMF in remission, FMF at the first day of an attack, FMF 7 days after the start of the attack, and healthy controls. Four females and two males were included. All patients had FMF with high severity score, 2.8 ± 0.4 (0-3). The mean age was 31.6 ± 6.2. The mean age at onset was 9.3 ± 9.3. The mean colchicine dose was 2.6 mg ± 0.4. The expression of Foxp3 7 days after the attacks was significantly higher than in FMF at the first day of the attack, FMF in remission, and healthy controls 10.08 ± 2.36 vs. 7.005 ± 0.3 vs. 5.3 ± 1.06 vs. 4.44 ± 1.8; p < 0.05 (Fig.1). The percentage of T-regs in peripheral blood was not statistically different between the four groups. Theexpression of Foxp3 by T-regs increases 7 days after attacks of FMF. Anti-inflammatory cytokines interleukin-10 and TGF-β are known to activate T-regs and have been reported to increase in FMF attacks in line with the present findings. It is suggested that T-regs may have a role in terminating FMF attacks.

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Cytokine profile of Armenian patients with Familial Mediterranean fever

Cited by 63 publications

References 10 publications

Effects of different Familial Mediterranean Fever gene mutations and in vitro Colchicine treatment on Peripheral Blood Mononuclear Cells production of IL-6

Effects of different Familial Mediterranean Fever gene mutations and in vitro Colchicine treatment on Peripheral Blood Mononuclear Cells production of IL-6

Diminished IL-10 production is Associated with Impaired Versatility of Monocytes in Familiar Mediterranean Fever

The role of regulatory T cells in familial Mediterranean fever (FMF)

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