Beneficial effect of the inosine monophosphate dehydrogenase inhibitor mycophenolate mofetil on survival and severity of glomerulonephritis in systemic lupus erythematosus (SLE)-prone MRLlpr/lpr mice.
The aim of the present study was to evaluate the therapeutic effect of mycophenolate mofetil (MMF) on the course of disease in SLE-prone MRLlpr/lpr mice. Three-months-old mice displaying clinical symptoms of glomerulonephritis were given MMF (100 mg/kg per day) orally via the drinking water. Control mice received i.p. injections of cyclophosphamide (CYC) (1.8 mg/mouse per week) or saline. Survival, albuminuria and haematuria, immunoglobulin levels and anti-dsDNA antibodies in serum, frequencies of immunoglobulin-producing B lymphocytes and glomerular deposits of immunoglobulin and C3 were analysed. The results showed that MMF treatment significantly prolonged survival and reduced the occurrence of albuminuria and haematuria in MRLlpr/lpr mice. In addition, the number of immunoglobulin-producing B cells and serum levels of IgG and IgG anti-dsDNA antibodies were reduced after MMF and CYC treatment. MMF treatment significantly reduced the extent of deposition of C3 in glomeruli. We conclude that the reduced severity of glomerulonephritis following treatment of lupus-prone mice with MMF was as efficacious as that of CYC. These results warrant clinical trials of MMF in SLE patients with glomerulonephritis.
Jonsson
C A
CA
Department of Rheumatology, University of Göteborg, Sweden. charlotte.jonsson@immuno.gu.se
Svensson
L
L
Carlsten
H
H
D000477:Alkylating Agents / Q000627:therapeutic use; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D003520:Cyclophosphamide / Q000627:therapeutic use; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D007136:Immunoglobulins / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D000477:Alkylating Agents; D000974:Antibodies, Antinuclear; D004791:Enzyme Inhibitors; D007136:Immunoglobulins; D003520:Cyclophosphamide; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid