Gliclazide inhibits differentiation-associated biologic events in human monocyte-derived macrophages

We investigated the in vitro effect of gliclazide on human monocyte-derived macrophage scavenger receptor expression and activity, foam cell formation, and lipopolysaccharide-induced cytokine production. Differentiation of human monocytes into macrophages in the presence of gliclazide (1-10 μg/mL) decreased CD36 expression by 20% to 50%, with maximal effect occurring at 2.5 μg/mL (P < .05). This effect was mimicked by vitamin E (50 μmol/L) and N-acetyl-l-cysteine (10 mmol/L). Incubation of the cells with gliclazide and N-acetyl-l-cysteine also reduced CD36 activity by 30% (P < .02). Despite these effects, neither gliclazide nor vitamin E did affect foam cell formation. In contrast, gliclazide significantly reduced lipopolysaccharide-stimulated macrophage tumor necrosis factor α and interleukin 6 secretion (P < .05). Overall, these data indicate that gliclazide, at concentrations in the therapeutic range, may regulate some key biologic events associated with the process of monocyte differentiation into macrophages.