Anti-inflammatory effects of rosuvastatin in healthy subjects

A prospective longitudinal study

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Aims: 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-, 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. Key findings: 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-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. Significance: The decline in tlr-4 expression on blood monocytes and TNF-plasma concentrations after 3 weeks of rosuvastatin treatment suggest a potential mechanism for the anti-inflammatory activity of rosuvastatin.

Original languageEnglish (US)
Pages (from-to)1156-1160
Number of pages5
JournalCurrent Pharmaceutical Design
Volume20
Issue number7
DOIs
StatePublished - Mar 7 2014

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Longitudinal Studies
Healthy Volunteers
Anti-Inflammatory Agents
Prospective Studies
Toll-Like Receptor 4
Monocytes
Interleukin-8
Insulin-Like Growth Factor I
Interleukin-6
Cholesterol
Therapeutics
Hydroxymethylglutaryl-CoA Reductase Inhibitors
VLDL Cholesterol
Nonparametric Statistics
Rosuvastatin Calcium
C-Reactive Protein
LDL Cholesterol
HDL Cholesterol
Lipopolysaccharides
Flow Cytometry

Keywords

  • Inflammation
  • Rosuvastatin
  • Toll-like receptor-4

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

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title = "Anti-inflammatory effects of rosuvastatin in healthy subjects: A prospective longitudinal study",
abstract = "Aims: 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-, 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. Key findings: 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-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. Significance: The decline in tlr-4 expression on blood monocytes and TNF-plasma concentrations after 3 weeks of rosuvastatin treatment suggest a potential mechanism for the anti-inflammatory activity of rosuvastatin.",
keywords = "Inflammation, Rosuvastatin, Toll-like receptor-4",
author = "McGuire, {Timothy R} and Kalil, {Andre C} and Dobesh, {Paul P} and Klepser, {Donald G} and Olsen, {Keith M.}",
year = "2014",
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day = "7",
doi = "10.2174/1381612820666140127163313",
language = "English (US)",
volume = "20",
pages = "1156--1160",
journal = "Current Pharmaceutical Design",
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TY - JOUR

T1 - Anti-inflammatory effects of rosuvastatin in healthy subjects

T2 - A prospective longitudinal study

AU - McGuire, Timothy R

AU - Kalil, Andre C

AU - Dobesh, Paul P

AU - Klepser, Donald G

AU - Olsen, Keith M.

PY - 2014/3/7

Y1 - 2014/3/7

N2 - Aims: 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-, 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. Key findings: 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-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. Significance: The decline in tlr-4 expression on blood monocytes and TNF-plasma concentrations after 3 weeks of rosuvastatin treatment suggest a potential mechanism for the anti-inflammatory activity of rosuvastatin.

AB - Aims: 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-, 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. Key findings: 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-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. Significance: The decline in tlr-4 expression on blood monocytes and TNF-plasma concentrations after 3 weeks of rosuvastatin treatment suggest a potential mechanism for the anti-inflammatory activity of rosuvastatin.

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KW - Rosuvastatin

KW - Toll-like receptor-4

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