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 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.
Brumeanu
Teodor-D
TD
Department of Medicine, Division of Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, A3074, Bethesda, MD 20814, USA. tbrumeanu@usuhs.mil
Goldstein
Robert
R
Casares
Sofia
S
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D000069059:Atorvastatin; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000517:prevention & control; D002784:Cholesterol / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000517:prevention & control; D015536:Down-Regulation / Q000276:immunology*; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin