Atorvastatin Inhibited ROS Generation And Increased IL-1β And IL-6 Release By Mononuclear Cells From Diabetic Patients

BACKGROUND: Atorvastatin (ATV) inhibits the conversion of 3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-CoA) to mevalonate formation and promotes lowering of the LDL cholesterol fraction. However, ATV exhibits pleiotropic metabolic actions beyond cholesterol-lowering properties. OBJECTIVE: We aimed to evaluate the effect of ATV on oxidizing species generation and cytokine secretion in Peripheral Blood Mononuclear Cells (PBMNC) of Type 2 Diabetes Mellitus (T2DM) patients in comparison to healthy control. METHODS: Both NADPH-oxidase-dependent and mitochondrial ROS generation were assessed by chemoluminescence luminol-dependent assay and fluorometric experiment, using Dichlorofluorescein Assay (DCFH-DA), respectively. IL-1β and IL-6 were quantified by classical ELISA. RESULTS: ATV inhibited NADPH-oxidase dependent ROS generation, but showed no effect on mitochondrial ROS generation and activated IL-1β and IL-6 secretions in PBMNC from control and T2DM patients. ROS generation and cytokine secretion in the presence of an inhibitor of Protein Kinase Cβ (iPKCβ) and ATV led to similar results. The secretion of IL-1β, PDB-induced in the presence of iPKCβ, but not ATV, was increased. ATV and iPKCβ exacerbated PDB-induced IL-6 secretion. LPS activated the secretion of IL-1β and IL-6 which was potentiated by ATV. CONCLUSION: ATV inhibited ROS generation and activated IL-1 β/IL-6 secretion in PBMNC of diabetes patients. Its effect was not affected by the hyperglycemia.