Simvastatin down-regulates the production of Interleukin-8 by neutrophil leukocytes from dyslipidemic patients

Abstract

BackgroundNeutrophil (PMN) leukocytes participate to the initial phases of atherosclerosis through the release of Interleukin 8 (CxCL8; IL-8) that contribute to amplification of inflammation. Aim of the study is to investigate the production of IL-8 by PMN leukocytes from dyslipidemic patients treated with simvastatin.MethodsIn 15 dyslipidemic subjects with moderately increased cardiovascular risk, assessed by Framingham Risk Score, blood samples were obtain to investigate PMNs IL-8 production [at baseline and after N-formyl-Met-Leu-Phe (fMLP) stimulation] before and after long-term (1-year) simvastatin treatment.ResultsThe resting release of IL-8 was higher in dyslipidemic patients at baseline when compared with control subjects (p < 0.05). One year of treatment was significantly associated with reduced IL-8 production (p < 0.01). Moreover, the fMLP-induced IL-8 production in dyslipidemic untreated patients was higher than that of controls (p < 0.05) and was reduced after simvastatin treatment (p < 0.01). IL-8 release after 1 year of treatment was reduced to levels which were lower than those observed in control subjects both for resting and stimulated cytokine production (p < 0.01).ConclusionsProlonged treatment with simvastatin is associated with a reduction of IL-8 production, suggesting the possibility of statin to modulate the pro-inflammatory response in PMNs of patients with moderately increased cardiovascular risk.

The Role of Inflammation in Myocardial Infarction

“…On the other hand, atorvastatin inhibits neutrophil infiltration in the early phase of the atherosclerotic buildup via nitric oxide, and this appears to be independent of any lowering effects on the cholesterol levels [151]. Recent studies on leukocytes isolated from dyslipidemic patients are showing that simvastatin reduced the proinflammatory chemokine IL-8 [152]. In addition, combinational use of an Angiotensin-II receptor blockers [ARB] (telmisartan) with a statin (rosuvastatin) in patients with carotid atherosclerosis showed a remarkable effect on suppressing a wide range of inflammatory factors including IL-1β/2/6/10/17/23, TNF-α, CRP, and MCP-1 [153].…”

Protective Effects of Simvastatin and Hesperidin against Complete Freund's Adjuvant-Induced Rheumatoid Arthritis in Rats

“…Simvastatin was also reported to suppress lymphocyte activation in patients with hypertriglyceridemia [44] . Marino et al [45] reported that simvastatin could suppress IL-8 production from neutrophils in dyslipidemic patients. Simvastatin was also reported to protect dopaminergic neurons in rats with experimentally induced Parkinsonism via suppression of TNF-α production [46] .…”

The Toxicological Mechanisms of Environmental Soot (Black Carbon) and Carbon Black: Focus on Oxidative Stress and Inflammatory Pathways

“…Simvastatin has been shown to affect many adverse functions of neutrophils. In a recent study, it has been shown that simvastatin downregulated secretion of interleukin-8 (IL-8) by neutrophils from the dyslipidemic patients ( 281 ). In addition to targeting specialized cells, some other miscellaneous strategies can also be used for the possible management of soot- and CB-associated toxicity.…”