Effect of combining ACE inhibitor and statin in lupus-prone mice.
MRL-Fas(lpr) mice spontaneously develop a systemic autoimmune disease resembling human systemic lupus erythematosus. The glomerulonephritis in MRL-Fas(lpr) 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-Fas(lpr) 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-Fas(lpr) 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.
Shimazu
Hideki
H
Department of Nephrology and Rheumatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
Kinoshita
Koji
K
Hino
Shoichi
S
Yano
Tomohiro
T
Kishimoto
Kazuya
K
Nagare
Yasuaki
Y
Nozaki
Yuji
Y
Sugiyama
Masafumi
M
Ikoma
Shinya
S
Funauchi
Masanori
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001794:Blood Pressure; D016207:Cytokines / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D048289:Imidazolidines / Q000008:administration & dosage*; D007074:Immunoglobulin G / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008181:Lupus Nephritis / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D017035:Pravastatin / Q000008:administration & dosage*; D011507:Proteinuria / Q000188:drug therapy / Q000517:prevention & control; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms
D000806:Angiotensin-Converting Enzyme Inhibitors; D000974:Antibodies, Antinuclear; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D048289:Imidazolidines; D007074:Immunoglobulin G; C065166:imidapril; D017035:Pravastatin