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'scomplete 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. Prctreatmcnt 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 delectable 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 palhogcncsis of EAG.