Immunomodulatory Effects of Statins

Abstract

Abstract. Clinical trials with statins have demonstrated a marked reduction of cardiovascular mortality. However, it remains controversial whether these clinical benefits stem from powerful cholesterol-lowering effects of statins or whether they are due in part to their cholesterol-independent effects on vascular function, plaque growth, plaque rupture, or thrombosis. The identification of several mechanisms through which statins decrease the recruitment of monocytes and T cells into the arterial wall and inhibit T cell activation and proliferation in vitro have prompted speculations that immunomodulatory effects of statins may be beneficial in recipients of organ transplants. Hypercholesterolemia is frequent in these patients, and delayed-type hypersensitivity reactions in the arterial walls of the graft may be compounded by chronic inflammation associated with conventional atherogenesis. To assess the potential clinical relevance of immunomodulatory effects of statins, the role of the immune system in atherogenesis and the effects of statins in vitro in experimental models and in clinical trials will be reviewed. It is concluded that despite solid in vitro evidence, clinical evidence for an independent immunosuppressive effect of statins in organ transplant patients is presently insufficient; however, further investigation of their in vivo occurrence and clinical relevance is warranted.

Geranylgeraniol Regulates Negatively Caspase-1 Autoprocessing: Implication in the Th1 Response against Mycobacterium tuberculosis

“…Because the benefit of such a treatment is greater than expected in terms of the reduction of low density lipoprotein cholesterol levels produced, it has been proposed that statins exert actions beyond that of simply lowering cholesterol. In keeping with this, some effects of statins on immune function have been reported (41)(42)(43)(44)(45). In PBMC, we demonstrated that fluvastatin induces caspase-1 activation and a small secretion of IL-1␤, IL-18, and IFN-␥.…”

Effects of simvastatin on markers of inflammation, oxidative stress and endothelial cell apoptosis in patients on chronic hemodialysis

“…HMCoA-reductase inhibitors, or statins, are potent lipid lowering drugs. Intensive clinical end-point trials in the general population have demonstrated that they effectively reduce lipid levels, the incidence of cardiovascular disease (CVD), and cardiovascular mortality [2][3][4] . In the last few years, there has been unanimity that the benefits from their use are ascribable only in part to their lipid-lowering effects 5) .…”

Comparative effects of pitavastatin and probucol on oxidative stress, Cu/Zn superoxide dismutase, PPAR-γ, and aortic stiffness in hypercholesterolemia

“…The inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductases (statins) have favorable effects on the progression of atherosclerosis and plaque instability, independent of their lipid-lowering activity (26,28,36,44). These "pleiotropic effects" of statins include improvement of endothelial function, antithrombotic actions, plaque stabilization, reduction of the vascular inflammatory process, and an antioxidant function through the inhibition of NAD(P)H oxidase or the increase in SOD activity (3,6,26,32).…”