The online version of this article (doi:10.1186/1471-2261-14-37) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
FM, AMM and LG: design, data collection, drawing the manuscript, data analysis and statistics. All authors: design, critical revision of article and approval of article.
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.
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.
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).
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.
Lefer AM, Lefer DJ: The role of nitric oxide and cell adhesion molecules on the microcirculation in ischaemia-reperfusion. Cardiovasc Res. 1996, 2: 743-751. CrossRef
Kristal B, Shurtz-Swirski R, Chezar J, Manaster J, Levy R, Shapiro G, Weissman I, Shasha SM, Sela S: Participation of peripheral polymorphonuclear leukocytes in the oxidative stress and inflammation in patients with essential hypertension. Am J Hypertens. 1998, 11: 921-928. 10.1016/S0895-7061(98)00099-5. CrossRefPubMed
Sela S, Shurtz-Swirski R, Cohen-Mazor M, Mazor R, Chezar J, Shapiro G, Hassan K, Shkolnik G, Geron R, Kristal B: The primed peripheral polymorphonuclear leukocytes – a culprit underlying chronic low-grade inflammation and systemic oxidative stress in chronic kidney disease. J Am Soc Nephrol. 2005, 16: 2431-2438. 10.1681/ASN.2004110929. CrossRefPubMed
Marino F, Guasti L, Cosentino M, Ferrari M, Rasini E, Maio RC, Cimpanelli MG, Cereda E, Crespi C, Simoni C, Restelli D, Venco A, Lecchini S: Angiotensin II type 1 receptor expression in polymorphonuclear leukocytes from high-risk subjects: changes after treatment with simvastatin. J Cardiovasc Pharmacol. 2007, 49: 299-305. 10.1097/FJC.0b013e31803d35ce. CrossRefPubMed
Guasti L, Marino F, Cosentino M, Cimpanelli M, Maio RC, Klersy C, Crespi C, Restelli D, Simoni C, Franzetti I, Gaudio G, Marnini P, Grandi AM, Lecchini S, Venco A: Simvastatin treatment modifies polymorphonuclear leukocyte function in high-risk subjects: a longitudinal study. J Hypertens. 2006, 24: 2423-2440. 10.1097/01.hjh.0000251903.62804.77. CrossRefPubMed
Guasti L, Marino F, Cosentino M, Maio RC, Rasini E, Ferrari M, Castiglioni L, Klersy C, Gaudio G, Grandi AM, Lecchini S, Venco A: Prolonged Statin-associated Reduction in Neutrophil Reactive Oxygen Species and Angiotensin II Type 1 Receptor Expression: 1-Year Follow-up. Eur Heart J. 2008, 29: 1118-1126. 10.1093/eurheartj/ehn138. CrossRefPubMed
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001, 285: 2486-2497. 10.1001/jama.285.19.2486. CrossRef
Libby P, Lichtman AH, Hansson GK: Immune effector mechanisms implicated in atherosclerosis: from mice to humans. Immunity. 2013, 39 (2): 413-10.1016/j.immuni.2013.07.015. CrossRef
Matsushima K, Baldwin ET, Mukaida N: Interleukin-8 and MCAF: novel leukocyte recruitment and activating cytokines. Chem Immunol. 1992, 51: 236-265. PubMed
Boekholdt SM, Peters RJ, Hack CE, Day NE, Luben R, Bingham SA, Wareham NJ, Reitsma PH, Khaw KT: IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women. Arterioscl Thromb Vasc Biol. 2004, 24: 1503-1508. 10.1161/01.ATV.0000134294.54422.2e. CrossRefPubMed
Rezaie-Majd A, Prager GW, Bucek RA, Schernthaner GH, Maca T, Kress HG, Valent P, Binder BR, Minar E, Baghestanian M: Simvastatin reduces the expression of adhesion molecules in circulating monocytes from hypercholesterolemic patients. Arterioscler Thromb Vasc Biol. 2003, 23: 397-403. 10.1161/01.ATV.0000059384.34874.F0. CrossRefPubMed
Romano M, Diomede L, Sironi M, Massimiliano L, Sottocorno M, Polentarutti N, Guglielmotti A, Albani D, Bruno A, Fruscella P, Salmona M, Vecchi A, Pinza M, Mantovani A: Inhibition of monocyte chemotactic protein-1 synthesis by statins. Lab Invest. 2000, 80: 1095-1100. 10.1038/labinvest.3780115. CrossRefPubMed
Yoshida M, Sawada T, Ishii H, Gerszten RE, Rosenzweig A, Gimbrone MA, Yasukochi Y, Numano F: Hmg-CoA reductase inhibitor modulates monocyte-endothelial cell interaction under physiological flow conditions in vitro: involvement of Rho GTPase-dependent mechanism. Arterioscler Thromb Vasc Biol. 2001, 21: 1165-1171. 10.1161/hq0701.092143. CrossRefPubMed
Rezaie-Majd A, Maca T, Bucek RA, Valent P, Müller MR, Husslein P, Kashanipour A, Minar E, Baghestanian M: Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients. Arterioscler Thromb Vasc Biol. 2002, 22: 1194-1199. 10.1161/01.ATV.0000022694.16328.CC. CrossRefPubMed
- Simvastatin down-regulates the production of Interleukin-8 by neutrophil leukocytes from dyslipidemic patients
Andrea Maria Maresca
Ramona C Maio
Laura Robustelli Test
Anna Maria Grandi
- BioMed Central
Neu im Fachgebiet Kardiologie
Mail Icon II