Engaging anti-inflammatory mechanisms and triggering inflammatory effector apoptosis during Familial Mediterranean Fever attack

• Published in: Inflammation research 2008-01, Vol.57 (2), p.65-74
• Main Authors: Davtyan, T K, Hakobyan, G S, Avetisyan, SA, Harutyunyan, V A
• Format: Article
• Language: English
• ISSN: 1023-3830
• DOI: 10.1007/sOOO11-007-7074-6

Objective: To investigate endotoxin-induced tolerance, intracellular cytokine synthesis polarization and mono-cyte apoptosis during Familial Mediterranean Fever (FMF). Methods: Lipopolysaccharide (LPS)-induced tolerance, intracellular cytokine synthesis and monocyte apoptosis were determined in FMF patients by flow cytometry using whole blood cell culture technique. Results: Endotoxin homo- and cross-tolerance, detected as the percentage of TNF- alpha synthesizing monocytes, developed in whole blood preparations of patients in attack period, but not during remission. The induction of anti-inflammatory cytokine synthesis polarization and enhancement of iodine-lithium- alpha -dextrin- and LPS-induced monocyte apoptosis was observed in FMF patients during the attack, whereas monocytes from patients in remission period exhibited pro-inflammatory cytokine polarization and resistance to the repeated LPS-induced apoptosis. Colchicine induced anti-inflammatory cytokine synthesis and caused down-modulation of monocyte apoptosis, whereas cytokines did not alter LPS-induced monocyte apoptosis. Conclusion: The self-limited nature of attacks during FMF may represent periods of inflammation resolution compensatory to continued sub-clinical inflammation during the remission.