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Published in: Critical Care 1/2006

01-02-2006 | Commentary

Do statins have a role in preventing or treating sepsis?

Authors: Victor Novack, Marius Terblanche, Yaniv Almog

Published in: Critical Care | Issue 1/2006

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Abstract

Statins have a variety of properties that are independent of their lipid lowering ability. These anti-inflammatory, antioxidant, immunomodulatory, and antiapoptotic features have been collectively referred to as pleiotropic effects. Severe sepsis is an intense infection-induced inflammatory syndrome that ultimately results in organ dysfunction. Because so many cascades are triggered during sepsis, merely blocking a single component may be insufficient to arrest the inflammatory process. A growing body of evidence suggests that statins may indeed have a protective effect against severe sepsis and reduce the rate of infection-related mortality. This novel primary prevention concept may have far-reaching implications for the future management of serious infections. Moreover, it was recently shown that statins potentially improve outcome after the onset of sepsis. The stage is now set for randomized clinical trials that will determine the precise role, if any, that statins may have in preventing and treating sepsis.
Literature
1.
go back to reference Martin GS, Mannino DM, Eaton S, Moss M: The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003, 348: 1546-1554. 10.1056/NEJMoa022139CrossRefPubMed Martin GS, Mannino DM, Eaton S, Moss M: The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003, 348: 1546-1554. 10.1056/NEJMoa022139CrossRefPubMed
2.
go back to reference Riedemann NC, Guo RF, Ward PA: Novel strategies for the treatment of sepsis. Nat Med 2003, 9: 517-524. 10.1038/nm0503-517CrossRefPubMed Riedemann NC, Guo RF, Ward PA: Novel strategies for the treatment of sepsis. Nat Med 2003, 9: 517-524. 10.1038/nm0503-517CrossRefPubMed
3.
go back to reference Osler W: The Evolution of Modern Medicine, 1904. Reprinted in 2005. Whitefish, MT: Kessinger Publishing; 2005. Osler W: The Evolution of Modern Medicine, 1904. Reprinted in 2005. Whitefish, MT: Kessinger Publishing; 2005.
4.
go back to reference Almog Y: Statins, inflammation, and sepsis: hypothesis. Chest 2003, 124: 740-743. 10.1378/chest.124.2.740CrossRefPubMed Almog Y: Statins, inflammation, and sepsis: hypothesis. Chest 2003, 124: 740-743. 10.1378/chest.124.2.740CrossRefPubMed
5.
go back to reference Blanco-Colio LM, Tunon J, Martin-Ventura JL, Egido J: Anti-inflammatory and immunomodulatory effects of statins. Kidney Int 2003, 63: 12-23. 10.1046/j.1523-1755.2003.00744.xCrossRefPubMed Blanco-Colio LM, Tunon J, Martin-Ventura JL, Egido J: Anti-inflammatory and immunomodulatory effects of statins. Kidney Int 2003, 63: 12-23. 10.1046/j.1523-1755.2003.00744.xCrossRefPubMed
6.
go back to reference Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U: Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med 2001, 7: 687-692. 10.1038/89058CrossRefPubMed Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U: Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med 2001, 7: 687-692. 10.1038/89058CrossRefPubMed
7.
go back to reference Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto AM Jr: Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001, 344: 1959-1965. 10.1056/NEJM200106283442601CrossRefPubMed Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto AM Jr: Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001, 344: 1959-1965. 10.1056/NEJM200106283442601CrossRefPubMed
8.
go back to reference Steiner S, Speidl WS, Pleiner J, Seidinger D, Zorn G, Kaun C, Wojta J, Huber K, Minar E, Wolzt M, et al.: Simvastatin blunts endotoxin-induced tissue factor in vivo. Circulation 2005, 111: 1841-1846. 10.1161/01.CIR.0000158665.27783.0CCrossRefPubMed Steiner S, Speidl WS, Pleiner J, Seidinger D, Zorn G, Kaun C, Wojta J, Huber K, Minar E, Wolzt M, et al.: Simvastatin blunts endotoxin-induced tissue factor in vivo. Circulation 2005, 111: 1841-1846. 10.1161/01.CIR.0000158665.27783.0CCrossRefPubMed
9.
go back to reference Dangas G, Badimon JJ, Smith DA, Unger AH, Levine D, Shao JH, Meraj P, Fier C, Fallon JT, Ambrose JA: Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile. J Am Coll Cardiol 1999, 33: 1294-1304. 10.1016/S0735-1097(99)00018-2CrossRefPubMed Dangas G, Badimon JJ, Smith DA, Unger AH, Levine D, Shao JH, Meraj P, Fier C, Fallon JT, Ambrose JA: Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile. J Am Coll Cardiol 1999, 33: 1294-1304. 10.1016/S0735-1097(99)00018-2CrossRefPubMed
10.
go back to reference Lee TS, Chang CC, Zhu Y, Shyy JY: Simvastatin induces heme oxygenase-1: a novel mechanism of vessel protection. Circulation 2004, 110: 1296-1302. 10.1161/01.CIR.0000140694.67251.9CCrossRefPubMed Lee TS, Chang CC, Zhu Y, Shyy JY: Simvastatin induces heme oxygenase-1: a novel mechanism of vessel protection. Circulation 2004, 110: 1296-1302. 10.1161/01.CIR.0000140694.67251.9CCrossRefPubMed
11.
go back to reference Grosser N, Hemmerle A, Berndt G, Erdmann K, Hinkelmann U, Schurgerc S, Wijayanti N, Immenschuh S, Schroder H: The antioxidant defense protein heme oxygenase 1 is a novel target for statins in endothelial cells. Free Radic Biol Med 2004, 37: 2064-2071. 10.1016/j.freeradbiomed.2004.09.009CrossRefPubMed Grosser N, Hemmerle A, Berndt G, Erdmann K, Hinkelmann U, Schurgerc S, Wijayanti N, Immenschuh S, Schroder H: The antioxidant defense protein heme oxygenase 1 is a novel target for statins in endothelial cells. Free Radic Biol Med 2004, 37: 2064-2071. 10.1016/j.freeradbiomed.2004.09.009CrossRefPubMed
12.
go back to reference Laufs U, Endres M, Custodis F, Gertz K, Nickenig G, Liao JK, Bohm M: Suppression of endothelial nitric oxide production after withdrawal of statin treatment is mediated by negative feedback regulation of rho GTPase gene transcription. Circulation 2000, 102: 3104-3110.CrossRefPubMed Laufs U, Endres M, Custodis F, Gertz K, Nickenig G, Liao JK, Bohm M: Suppression of endothelial nitric oxide production after withdrawal of statin treatment is mediated by negative feedback regulation of rho GTPase gene transcription. Circulation 2000, 102: 3104-3110.CrossRefPubMed
13.
go back to reference Wagner AH, Schwabe O, Hecker M: Atorvastatin inhibition of cytokine-inducible nitric oxide synthase expression in native endothelial cells in situ. Br J Pharmacol 2002, 136: 143-149. 10.1038/sj.bjp.0704678PubMedCentralCrossRefPubMed Wagner AH, Schwabe O, Hecker M: Atorvastatin inhibition of cytokine-inducible nitric oxide synthase expression in native endothelial cells in situ. Br J Pharmacol 2002, 136: 143-149. 10.1038/sj.bjp.0704678PubMedCentralCrossRefPubMed
14.
go back to reference Giusti-Paiva A, Martinez MR, Felix JV, da Rocha MJ, Carnio EC, Elias LL, Antunes-Rodrigues J: Simvastatin decreases nitric oxide overproduction and reverts the impaired vascular responsiveness induced by endotoxic shock in rats. Shock 2004, 271-275. 10.1097/10.shk.0000115756.74059.ce Giusti-Paiva A, Martinez MR, Felix JV, da Rocha MJ, Carnio EC, Elias LL, Antunes-Rodrigues J: Simvastatin decreases nitric oxide overproduction and reverts the impaired vascular responsiveness induced by endotoxic shock in rats. Shock 2004, 271-275. 10.1097/10.shk.0000115756.74059.ce
15.
go back to reference Pleiner J, Schaller G, Mittermayer F, Zorn S, Marsik C, Polterauer S, Kapiotis S, Wolzt M: Simvastatin prevents vascular hyporeactivity during inflammation. Circulation 2004, 110: 3349-3354. 10.1161/01.CIR.0000147774.90396.EDCrossRefPubMed Pleiner J, Schaller G, Mittermayer F, Zorn S, Marsik C, Polterauer S, Kapiotis S, Wolzt M: Simvastatin prevents vascular hyporeactivity during inflammation. Circulation 2004, 110: 3349-3354. 10.1161/01.CIR.0000147774.90396.EDCrossRefPubMed
16.
go back to reference Merx MW, Liehn EA, Janssens U, Lutticken R, Schrader J, Hanrath P, Weber C: HMG-CoA reductase inhibitor simvastatin profoundly improves survival in a murine model of sepsis. Circulation 2004, 109: 2560-2565. 10.1161/01.CIR.0000129774.09737.5BCrossRefPubMed Merx MW, Liehn EA, Janssens U, Lutticken R, Schrader J, Hanrath P, Weber C: HMG-CoA reductase inhibitor simvastatin profoundly improves survival in a murine model of sepsis. Circulation 2004, 109: 2560-2565. 10.1161/01.CIR.0000129774.09737.5BCrossRefPubMed
17.
go back to reference Merx M, Liehn E, Graf J, van de Sandt A, Schaltenbrand M, Schrader J, Hanrath P, Weber C: Statin treatment after onset of sepsis in a murine model improves survival. Circulation 2005, 112: 117-124. 10.1161/CIRCULATIONAHA.104.502195CrossRefPubMed Merx M, Liehn E, Graf J, van de Sandt A, Schaltenbrand M, Schrader J, Hanrath P, Weber C: Statin treatment after onset of sepsis in a murine model improves survival. Circulation 2005, 112: 117-124. 10.1161/CIRCULATIONAHA.104.502195CrossRefPubMed
18.
go back to reference Almog Y, Shefer A, Novack V, Maimon N, Barski L, Eizinger M, Friger M, Zeller L, Danon A: Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation 2004, 110: 880-885. 10.1161/01.CIR.0000138932.17956.F1CrossRefPubMed Almog Y, Shefer A, Novack V, Maimon N, Barski L, Eizinger M, Friger M, Zeller L, Danon A: Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation 2004, 110: 880-885. 10.1161/01.CIR.0000138932.17956.F1CrossRefPubMed
Metadata
Title
Do statins have a role in preventing or treating sepsis?
Authors
Victor Novack
Marius Terblanche
Yaniv Almog
Publication date
01-02-2006
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2006
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc3972

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