Abstract
Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies to various nuclear antigens and high serum cholesterol levels. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors has been shown to have exhibited anti-inflammatory effects in several clinical trials. We conducted this study to evaluate the effect of rosuvastatin on inflammatory responses in MRL/lpr mice, a representative model of human SLE.
Methods MRL/lpr mice were intraperitoneally injected with rosuvastatin (10 mg/kg, n = 4) or vehicle [2% dimethyl sulfoxide (DMSO), n = 4] five times a week from 13 to 17 weeks of age. The serum levels of low-density lipoprotein (LDL) cholesterol and autoantibodies were measured, as well as the urine levels of albumin. Renal tissues were stained with HE and PAS for histopathological analysis. Concentrations of key inflammatory cytokines in serum were measured, and messenger RNA (mRNA) levels in target organs (kidney, spleen, and lymph nodes) were evaluated.
Results Rosuvastatin treatment significantly decreased serum LDL-cholesterol concentration in MRL/lpr mice. However, the treatment of rosuvastatin did not improve clinical manifestations nor the titers of autoantibody. In addition, serum inflammatory cytokines and proteinuria were not changed with treatment of rosuvastatin. Furthermore, histopathological analysis of the kidneys did not improve with rosuvastatin treatment. When assessing the expression of mRNA, the treatment with rosuvastatin decreased tumor necrosis alpha in spleen and kidney tissue, and interleukin-17 concentration in the kidney and lymph node of MRL/lpr mice.
Conclusions The treatment of rosuvastatin is insufficient to improve disease activity of SLE, although it can decrease inflammatory cytokines in the lymphoid organs and kidneys of MRL/lpr mice.
