Engaging anti-inflammatory mechanisms and triggering inflammatory effector apoptosis during Familial Mediterranean Fever attack.
OBJECTIVE
To investigate endotoxin-induced tolerance, intracellular cytokine synthesis polarization and monocyte 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 proinflammatory 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.


CONCLUSIONS
The self-limited nature of attacks during FMF may represent periods of inflammation resolution compensatory to continued sub-clinical inflammation during the remission.
Davtyan
T K
TK
Laboratory of Immunology and Virology, Armenicum Research Centre, CJSC Armenicum, Yerevan, Republic of Armenia. tigdav@excite.com.
Hakobyan
G S
GS
Avetisyan
S A
SA
Harutyunyan
V A
VA
D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins / Q000378:metabolism; D010505:Familial Mediterranean Fever / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D012074:Remission Induction
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides