Cyclosporin A in the prevention and treatment of experimental autoimmune glomerulonephritis in the brown Norway rat.
Experimental autoimmune glomerulonephritis (EAG) was induced in brown Norway (BN) rats by a single i.m. injection of collagenase-solubilized homologous glomerular basement membrane (GBM) in Freund's complete adjuvant. This model of anti-GBM disease is characterized by the development, over several weeks, of circulating and deposited anti-GBM antibodies, accompanied by albuminuria. We examined the effects of treatment with oral cyclosporin A (CsA) at different doses, starting at the time of immunization and during the course of the disease. Pretreatment with CsA 5 mg kg daily produced a moderate reduction in circulating anti-GBM antibody levels, reduced deposition of antibody on the GBM and decreased albuminuria. Doses of 10 and 20 mg/kg CsA produced a marked reduction in circulating antibody, absence of detectable deposited antibody and virtual absence of albuminuria. Renal function remained normal in CsA-treated and control animals. When CsA treatment was introduced at 2 or 4 weeks after immunization, there were significant effects on the subsequent autoimmune response and albuminuria at 10 and 20 mg/kg daily. These studies demonstrate that CsA in conventional doses has a therapeutic effect in this model of anti-GBM disease, and suggest a role for T lymphocytes in the pathogenesis of EAG.
Reynolds
J
J
Department of Medicine, Royal Postgraduate Medical School, London, England.
Cashman
S J
SJ
Evans
D J
DJ
Pusey
C D
CD
D000284:Administration, Oral; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology / Q000473:pathology; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001485:Basement Membrane / Q000276:immunology; D003524:Cyclosporins / Q000627:therapeutic use*; D005260:Female; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011863:Radioimmunoassay; D051381:Rats; D011914:Rats, Inbred BN
D003524:Cyclosporins