Statins attenuate sepsis.
If (1) 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitors (statins) block the rate-limiting step in cholesterol synthesis and promote the expression of low-density lipoprotein receptors, (2) "Gram-negative sepsis" results from an abundant systemic response to bacterial lipopolysaccharide (endotoxin), (3) triglyceride-rich lipoproteins can bind endotoxin and low-density lipoprotein receptors enhance the uptake of both of these molecules, and (4) low-density lipoprotein receptor internalization of lipoproteins and endotoxin co-opts a common transcriptional regulatory system (NF-kappaB) that results in reduced cell vulnerability to inflammation, then statins, in addition to their lipid-lowering capacity, enhance endotoxin clearance from the circulation and attenuate the septic response.
Department of Surgery, University of California, San Francisco-East Bay, 1411 E. 31st Street, Oakland, CA 94602, USA. spitzera@surgery.ucsf.edu
Austin L
AL
Spitzer
Hobart W
HW
Harris
D002784:Cholesterol / Q000096:biosynthesis; D016905:Gram-Negative Bacterial Infections / Q000150:complications; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000502:physiology*; D018805:Sepsis / Q000188:drug therapy* / Q000503:physiopathology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008070:Lipopolysaccharides; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D002784:Cholesterol