Simvastatin inhibits interleukin-6 release in human monocytes stimulated by C-reactive protein and lipopolysaccharide

Background The accumulating evidence suggests that C-reactive protein (CRP) may have direct inflammatory effects on the vascular wall and that statin therapy may have important non-lipid anti-inflammatory effects confirmed by decreasing serum inflammatory markers, such as CRP. However, the effect of simvastatin on interleukin-6 (IL-6) release in cultured human monocytes was not investigated. Design A prospective, human monocyte culture, simvastatin intervention study. Methods Monocytes were isolated from blood of healthy volunteers by the Ficoll density gradient and stimulated by broad concentrations of CRP (1-20 mug/ml) and lipopolysaccharide (LPS, 1-10 ng/ml) at indicated time points (0, 2, 4, 8, 16 and 24 h). Also 10(-8)-10(-6) mol/l simvastatin was coincubated with cells in the presence of CRP and LIPS. Measurements of IL-6 were performed from supernatants of cultured medium in duplicate, using a commercial assay kit. Results CRP and LIPS induced the rapid release of IL-6, with significantly elevated levels in cultured supernatants at 4 h in the CRP group and at 2 h in the LIPS group. The effects of CRP and LIPS on IL-6 release of monocytes were dose and time dependent. A greater than 11-fold increase of IL-6 in the CRP group (20 mug/ml) and a greater than 26-fold increase in the LPS group (10 ng/ml) were observed at 24 h compared with the control group (945.7+/-98.3 pg/ml compared with 94.3+/-12.4 pg/ml and 1720.4+/-690.1 pg/ml compared with 70.1+/-16.7 pg/ml, P<0.001, respectively). However, 10(-8)-10(-6) mol/l simvastatin inhibited significantly the production of IL-6 in monocytes stimulated by CRP and LPS in a dose-dependent manner, with the maximal inhibiting effect at a concentration of 10(-6) mol/l (945.7 +/- 98.3 pg/ml compared with 180.9 +/- 31.2 pg/ml and 1720.4 +/- 690.1 pg/ml compared with 824.0 +/- 206.2 pg/ml, P<0.001 respectively). Conclusions CRP and LIPS could induce IL-6 release in human monocytes and simvastatin could inhibit this response in a dose-dependent manner, which may provide an insight into the mechanisms of anti-inflammatory or anti-atherosclerotic actions of simvastatin.