Effect of combining ACE inhibitor and statin in lupus-prone mice

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2010-08, Vol.136 (2), p.188-196
• Main Authors: Shimazu, Hideki, Kinoshita, Koji, Hino, Shoichi, Yano, Tomohiro, Kishimoto, Kazuya, Nagare, Yasuaki, Nozaki, Yuji, Sugiyama, Masafumi, Ikoma, Shinya, Funauchi, Masanori
• Format: Article
• Language: English
• Subjects: ACEI; Allergy and Immunology; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Animals; Antibodies, Antinuclear - blood; Biological and medical sciences; Blood Pressure; Cytokines - metabolism; Drug Therapy, Combination; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Imidazolidines - administration & dosage; Immunoglobulin G - metabolism; Kidney; Kidney - immunology; Kidney - metabolism; Kidney - pathology; Lupus; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - immunology; Lupus Nephritis - drug therapy; Lupus Nephritis - immunology; Medical sciences; Mice; Mice, Inbred C3H; Mice, Inbred MRL lpr; Nephritis; Pravastatin - administration & dosage; Proteinuria - drug therapy; Proteinuria - prevention & control; Random Allocation; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Specific Pathogen-Free Organisms; Statin
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2010.03.008

Abstract MRL-Faslpr mice spontaneously develop a systemic autoimmune disease resembling human systemic lupus erythematosus. The glomerulonephritis in MRL-Faslpr mice is mediated by autoantibodies and autoreactive lymphocytes. To investigate the effect of combination therapy by angiotensin-converting enzyme inhibitor (ACEI) and hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin) for lupus nephritis, we treated MRL-Faslpr mice with imidapril, pravastatin or both agents. Compared with other groups, the mice treated by combination therapy survived longer and showed a significant reduction in proteinuria, renal pathology, including glomerular IgG deposit, and serum anti-DNA Ab. Furthermore, monocyte chemoattractant protein-1 (MCP-1) in the kidney was reduced significantly in the combination therapy group, compared with that in the control group. We conclude that combination therapy with ACEI and statin for MRL-Faslpr mice significantly alleviates autoimmune renal disorder and prolongs survival. These results suggest that combination therapy by ACEI and statin may represent a new approach to the treatment of patients with lupus.