Anti-inflammatory effects of rosuvastatin in healthy subjects: a prospective longitudinal study.
OBJECTIVE
The aims of this study were to determine a mechanism and general timeline for statin related anti-inflammatory activity.


METHODS
Healthy male subjects received rosuvastatin (20 mg daily) for 3 weeks. Blood samples before and after treatment were collected for clinical laboratories and research procedures. Toll-like receptor-4 (tlr-4) expression on blood monocytes was measured using flow cytometry before and after rosuvastatin treatment. Inflammatory molecules were measured before and after rosuvastatin and after blood samples were incubated for 3 hours with or without lipopolysaccharide. Plasma was collected and analyzed for IL-6, TNF-α, IL-8, IGF-1, and sCD14. Comparisons were made using Mann-Whitney rank sum test and paired Student's t-test with significance defined as p≤0.05.


RESULTS
The expression oftlr-4on blood monocytes was significantly lower after 3 weeks of rosuvastatin (p = 0.046). Consistent with the reduced expression of tlr-4, the TNF-α release from blood receiving LPS trended lower (p = 0.08). None of the other inflammatory markers (IL-8, sCD14, IL-6, IGF-1, C-reactive protein) were modified with rosuvastatin treatment. There were significant declines in total cholesterol (p<0.0001), low-density lipoprotein cholesterol (LDL-C) (p<0.0001), and total cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio (p<0.0001) after 3 weeks of treatment. There was no significant effect on triglycerides, very low-density lipoprotein cholesterol (VLDL-C), or HDL-C.


CONCLUSIONS
The decline in tlr-4 expression on blood monocytes and TNF-α plasma concentrations after 3 weeks of rosuvastatin treatment suggest a potential mechanism for the anti-inflammatory activity of rosuvastatin.
Timothy R
TR
McGuire
Andre C
AC
Kalil
Paul P
PP
Dobesh
Donald G
DG
Klepser
University of Nebraska Medical Center, Department of Pharmacy Practice, Omaha, NE 68198-6045. trmcguir@unmc.edu.
Keith M
KM
Olsen
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D005464:Fluorobenzenes / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008137:Longitudinal Studies; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000097:blood; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D005464:Fluorobenzenes; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011743:Pyrimidines; D013449:Sulfonamides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D000068718:Rosuvastatin Calcium; D002784:Cholesterol