Dexamethasone, colchicine and iodine-lithium-alpha-dextrin act differentially on the oxidative burst and endotoxin tolerance induction in vitro in patients with Behçet's disease.

Pro-inflammatory activation of innate immune cells, such as macrophages, and neutrophils in patients with Behçet's disease (BD) results in increased production of reactive oxygen species and enhanced adhesion to endothelial cells due to increased expression of adhesion receptors. We investigated the influence of dexamethasone (DEX), colchicine (Col), and iodine-lithium-alpha-dextrin (ILalphaD), during BD, on the respiratory burst of whole blood neutrophils and monocytes, CD11a/CD18 surface expression, monocyte endotoxin tolerance and cytokine synthesis in vitro. In BD patients we observed an increase of the spontaneous, N-formyl-Met-Leu-Phe- and LPS-induced respiratory burst of monocytes and neutrophils as well as up-regulation of neutrophil CD11a/CD18 surface expression. DEX, Col and ILalphaD in vitro differentially affected the stimulus-dependent oxidative burst of BD and caused the down-regulation of CD11a/CD18 surface expression in neutrophils but not monocytes. LPS homologous tolerance induction is not altered in BD. However, DEX and Col increased tolerance to LPS-induced TNF-alpha synthesis. ILalphaD down-regulated N-formyl-Met-Leu-Phe- and LPS-induced oxidative burst and CD14 receptor expression and increased monocyte cross-tolerance to LPS. DEX induced LPS-tolerance by restoring the ratio of INF-gamma and IL-4 production, while Col caused a dramatic increase in IL-4 synthesis by monocytes. DEX, Col and ILalphaD may limit the overwhelming inflammation by differentially affecting the monocyte activation program, shifting them from ''classically" into "alternatively'' activated monocytes and may have important implications for the treatment of BD.