Simvastatin treatment modifies polymorphonuclear leukocyte function in high-risk individuals: a longitudinal study

被引:32
作者
Guasti, Luigina [1 ]
Marino, Franca [1 ]
Cosentino, Marco [1 ]
Cimpanelli, Mariagrazia [1 ]
Maio, Ramona C. [1 ]
Klersy, Catherine [1 ]
Crespi, Chiara [1 ]
Restelli, Daniela [1 ]
Simoni, Cinzia [1 ]
Franzetti, Ivano [1 ]
Gaudio, Giovanni [1 ]
Marnini, Patrizio [1 ]
Grandi, Anna M. [1 ]
Lecchini, Sergio [1 ]
Venco, Achille [1 ]
机构
[1] Univ Insubria, Dept Clin Med, I-21100 Varese, Italy
关键词
human polymorphonuclear leukocytes; interleukin-8; reactive; oxygen species; statins;
D O I
10.1097/01.hjh.0000251903.62804.77
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Background Although extensive experimental evidence supports a primary role of polymorphonuclear leukocytes (PMNs) in atherosclerosis, few data exist concerning the functional properties of these cells and their pharmacological modulation in high-risk individuals. Objective The production of the proinflammatory chemokine interleukin-8 (IL-8), migration and chemotaxis, and reactive oxygen species (ROS) generation were investigated in a longitudinal study in PMNs obtained from high-risk individuals during statin treatment. As a secondary endpoint we compared PMN function of high-risk patients with that of controls. Methods and results PMNs were isolated from 21 high-risk individuals before treatment and 3 and 30 days after the beginning of simvastatin treatment, and from healthy controls. During treatment a significant reduction was observed both in resting (P = 0.009) and N-formyl-Met-Leu-Phe (fMLP)-stimulated (P = 0.008) IL-8 production, and in the chemotactic index (P = 0.038), whereas ROS generation did not significantly change. In comparison with cells from controls, PMNs obtained from patients before starting simvastatin treatment showed higher resting and fMLP-stimulated IL-8 release (P = 0.007 and P = 0.002, respectively) and ROS generation (resting, P = 0.009; and fMLP-stimulated, P = 0.046), whereas migration and the chemotactic index did not significantly differ. Conclusions An activation of neutrophils is present in high-risk individuals, shown by the enhanced production of IL-8, and increased ROS generation. The 4-week statin treatment is able to reduce the cell capability to produce IL-8, and to decrease chemotaxis, thus affecting the proinflammatory properties of PMNs.
引用
收藏
页码:2423 / 2430
页数:8
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