Different effects of simvastatin on ex vivo monocyte cytokine release in patients with hypercholesterolemia and impaired glucose tolerance.

The aim of our study was to compare the effect of simvastatin on systemic inflammation and monocyte secretory function between subjects with impaired glucose tolerance (IGT) and isolated hypercholesterolemia. We studied 26 patients with isolated IGT and 24 subjects with primary hypercholesterolemia, who were treated for 12 weeks with 20 mg of simvastatin daily. Plasma lipids, fasting and 2-h post-glucose load plasma glucose levels, HOMA ratio, glycated hemoglobin, plasma hsCRP levels and monocyte release of interleukin-6, interleukin-1β, MCP-1 and TNF-α were determined at entry, and after 4 and 12 weeks days of simvastatin administration. The control group included 25 age-, sex- and weight-matched dyslipidemia-free individuals with normal glucose tolerance. Compared to the control subjects, monocytes of both IGT and hypercholesterolemic subjects released greater amounts of interleukin-6, interleukin-1β, MCP-1 and TNF-α, and exhibited increased plasma hsCRP levels. No differences between IGT and hypercholesterolemic subjects in cytokine release and plasma hsCRP were observed. Despite improving lipid profile, simvastatin did not produce any effect on glucose metabolism markers in any treatment groups. In hypercholesterolemic subjects simvastatin reduced plasma hsCRP and monocyte cytokine secretion in a lipid- and glucose-independent manner, while in IGT subjects the drug produced only insignificant changes. Our results show that although low-grade systemic inflammation and monocyte secretory function are disturbed to a similar extent in isolated hypercholesterolemia and IGT, simvastatin exhibits a strong anti-inflammatory effect only in hypercholesterolemic patients.