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.