Statins as immunomodulators in systemic sclerosis

Systemic sclerosis (SSc) has the highest case-specific mortality among the rheumatic diseases. Vascular dysfunction and structural wall abnormalities are among the earliest and fundamental alterations in SSc. Statins have a number of immunomodulating effects on vascular wall cells, which may modify the progression of vascular injury. The aim of this study was to evaluate the potential efficacy of statin therapy in ameliorating endothelial dysfunction (ED) in SSc by investigating the effect of statins on some markers that reflect endothelial activation in SSc. Forty patients with SSc were randomized into two groups to receive 6 months' treatment with atorvastatin (n = 20; dose, 40 mg/day) or placebo (n = 20) as an adjuvant to existing therapy. Markers of ED including ET-1, plasma nitrate levels, and thrombomodulin (TM) were evaluated by the enzyme-linked immunosorbent assay (ELISA) technique. Fibrinogen, high-sensitivity C-reactive protein (hsCRP), ESR, lipid peroxide (LP), and malonylaldehyde (MDA) levels were also assessed. Brachial flow-mediated vasodilatation was assessed by ultrasonography. Patients were studied at base line and after 6 months of statin therapy. After 6 months of therapy, ET-1, ICAM-1, sE-selectin, vWF, fibrinogen, ESR, hsCRP as well as LP and MDA levels declined and NO increased significantly in the statin-treated SSc group when compared to the placebo-treated group. Endothelium-dependent vasodilatation (EDV) improved significantly in the atorvastatin-treated group. The findings of this study demonstrated statin-mediated improvements in the endothelial function of SSc patients as well as immunomodulating effects. Statins may thus prove to be an invaluable addition to the therapy of the vasculopathy of SSc.