Down-regulation of autoreactive T-cells by HMG CoA reductase inhibitors

The inhibitors of HMG CoA reductase (statins) are widely used as cholesterol-lowering drugs with excellent safety records in hypercholesterolemic patients. Statins exert pleiotropic effects on a variety of cells, and they were recently described as a new class of immune modulators. Depending on thei...

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Bibliographic Details
Published in:Clinical Immunology 2006-04, Vol.119 (1), p.1-12
Main Authors: Brumeanu, Teodor-D., Goldstein, Robert, Casares, Sofia
Format: Article
Language:English
Subjects:
Animals
Antigen-Presenting Cells - drug effects
Antigen-Presenting Cells - immunology
Atorvastatin Calcium
Autoimmune Diseases - drug therapy
Autoimmune Diseases - prevention & control
Autoimmunity
Biological and medical sciences
Cholesterol - biosynthesis
Diabetes Mellitus, Experimental - metabolism
Diabetes Mellitus, Experimental - pathology
Diabetes Mellitus, Experimental - prevention & control
Diabetes Mellitus, Type 1 - drug therapy
Diabetes Mellitus, Type 1 - prevention & control
Down-Regulation - immunology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Heptanoic Acids - pharmacology
Heptanoic Acids - therapeutic use
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Immunopathology
Medical sciences
Pyrroles - pharmacology
Pyrroles - therapeutic use
Statins
T cells
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Type 1 diabetes
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Summary:The inhibitors of HMG CoA reductase (statins) are widely used as cholesterol-lowering drugs with excellent safety records in hypercholesterolemic patients. Statins exert pleiotropic effects on a variety of cells, and they were recently described as a new class of immune modulators. Depending on their structure, dose, and route of administration, statins regulate the function of both the antigen-presenting cells and T-cells by HMG CoA reductase-dependent and independent mechanisms. Herein, we describe these mechanisms leading to prevention, amelioration, and reversal of autoimmune diseases. We also present data from our laboratories showing for the first time that in a double transgenic mouse model for autoimmune diabetes, atorvastatin (lipitor) prevented the onset of disease when administered in the neonatal period, and stabilized the glucose levels when administered in mice developing a mild form of diabetes.
ISSN:1521-6616
1521-7035
1365-2567
DOI:10.1016/j.clim.2005.11.007