Anti-inflammatory and immunomodulating properties of statins. An additional tool for the therapeutic approach of systemic autoimmune diseases?
Cardiovascular diseases secondary to accelerated atherosclerosis are now accepted as a cause of mortality and morbidity in patients suffering from systemic lupus erythematosus and rheumatoid arthritis. More recently, atherosclerosis is emerging as one of the most serious complications in the anti-phospholipid syndrome, although large epidemiological studies, such as those performed in lupus and rheumatoid arthritis patients, have not been performed up to now. Classical risk factors (dislipidemia, hypertension, diabetes, smoking, etc.) and steroid therapy cannot completely explain the high prevalence of cardiovascular complications in systemic autoimmune diseases. Since the modern view defines atherosclerosis as a chronic inflammatory disorder, it has been suggested that systemic inflammation and soluble immune mediators (circulating autoantibodies, immune-complexes, complement activation products) might play a role in accelerating vessel pathology. The main target appears to be the endothelium because of its ability to switch to a pro-adhesive, pro-inflammatory and pro-coagulant surface in response to these mediators. Recent advances in the knowledge of the pharmacology of statins have indicated that these drugs rather than to be simple cholesterol lowering molecules display a pleiotropic effects on several mechanisms involved in the atherosclerotic plaque formation. Their anti-inflammatory activity and particularly their ability to downregulate endothelial cell activation induced by different stimuli strongly suggest their possible use in conditions in which the systemic inflammation and the endothelial activation/damage are thought to represent key pathogenic mechanisms.
Meroni
Pier Luigi
PL
Allergy & Clinical Immunology Unit, Department of Internal Medicine, University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy. pierluigi.meroni@unimi.it
Luzzana
Cristina
C
Ventura
Donatella
D
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D012307:Risk Factors
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents