Short-term treatment with high-dose atorvastatin reduces LDL cholesterol but shows no anti-inflammatory effects in normolipidemic subjects with normal CRP levels.
The benefit in reducing cardiovascular risk with statins has been attributed both to cholesterol lowering and pleiotropic effects. These pleiotropic effects are thought to include attenuation of the inflammatory response due to reduced prenylation of proteins in the inflammatory cascade. We conducted studies in normolipidemic subjects to determine if treatment with high-dose (80 mg) atorvastatin could reduce circulating levels of inflammatory markers. We also determined whether high-dose atorvastatin affected the inflammatory response of monocytes stimulated with lipopolysaccharide (LPS) ex vivo. We found that treatment with atorvastatin rapidly and significantly reduced plasma low-density lipoprotein (LDL) cholesterol levels in subjects treated for 2 weeks. However, statin treatment had no discernible effect on plasma levels of the inflammatory markers high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-alpha, or interleukin (IL-6) and no effect on the cytokine response of monocytes following ex vivo stimulation with LPS. High-dose atorvastatin treatment of normolipidemic subjects with normal C-reactive protein levels has no effect on the inflammatory response assessed by monocyte stimulation with LPS ex vivo despite significant reductions in LDL cholesterol levels.
Millar
John S
JS
The Institute for Translational Medicine and Therapeutics, The University of Pennsylvania, Philadelphia, USA. jsmillar@mail.med.upenn.edu
Ky
Bonnie
B
Wolfe
Megan L
ML
Pruscino
Leticia
L
Baer
Amanda
A
Rader
Daniel J
DJ
D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001053:Apolipoproteins / Q000097:blood; D000069059:Atorvastatin; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D015243:Cholesterol, VLDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
D000924:Anticholesteremic Agents; D001053:Apolipoproteins; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D006538:Heptanoic Acids; D011758:Pyrroles; D002097:C-Reactive Protein; D000069059:Atorvastatin