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

Abstract

Background: Neutrophil (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.

Methods: In 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.

Results: The 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).

Conclusions: Prolonged 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.

Figure 1

IL-8 production in resting (left panel) and fMLP-induced (right panel) PMNs from dyslipidemic subjects before (baseline) and during statin treatment. Horizontal lines represent the median values, boxes represent the 25^th-75^th percentiles, and vertical bars the minimum and maximum values. For comparison, data obtained in healthy controls are also shown: median values (solid lines) with 25^th-75^th percentiles (dotted lines). * = P < 0.05 and ** = P < 0.01 vs control subjects. # = P < 0.01 vs baseline.