Considerable evidence implicates a role for interleukin-1 beta (IL-1β) in the pathogenesis of atherosclerosis1 revealing its potential as a novel therapeutic target. Statins are known to have anti-inflammatory effects,2 however the specific mechanisms remain to be established. To test the anti-inflammatory effects of simvastatin, PBMCs were isolated from healthy donors and treated in vitro with simvastatin (100 µM) or from hyperlipidaemic patients at baseline and following 8 weeks simvastatin (10–20 mg) daily treatment. PBMCs were then stimulated with LPS (100 ng/ml) for 3 hour followed by cholesterol crystal (CC) (1 mg/ml) stimulation overnight to activate the NLRP3 inflammasome complex involved in processing IL-1β to its mature secreted form. IL-Iβ levels in the supernatants form PBMCs was measured by ELISA. All experiments carried out were approved by the Medical Research Ethics Committees at St James Hospital/AMNCH, Dublin 8, Ireland and comply fully with the Declaration of Helsinki. Patients (n=9) taking simvastatin (10–20 mg daily) over 8 weeks exhibited reduced LDL cholesterol, (4.87±0.76 mmol/L) pre vs (3.78±0.67 mmol/L) post statin treatment. Simvastatin treatment also reduced levels of IL-1β secretion by PBMCs, when stimulated with LPS and CC, (5.27±0.6 ng/ml) pre vs (4.27±0.5 ng/ml) post statin treatment. Similarly, in vitro treatment of PBMCs with simvastatin (100 µM) reduced IL-1β secretion upon activation with LPS and CC, (2.37±0.17 ng/ml) control vs (0.64±0.06 ng/ml) simvastatin treatment. Values presented are mean ±sem. We have demonstrated that CC induced IL-1β release by PBMCs from hyperlipidaemic patients, is reduced after treatment with simvastatin. These data identify a previously unappreciated beneficial role for statin therapy in atherosclerotic patients.
. Duewell P, et al. Nature2010;464:1357–61.
. Arslan F, et al. Circ Res2008;103:334–6.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.