Cyclosporin A in the prevention and treatment of experimental autoimmune glomerulonephritis in the brown Norway rat

J Reynolds, SJ Cashman, DJ Evans… - Clinical & …, 1991 - academic.oup.com
J Reynolds, SJ Cashman, DJ Evans, CD Pusey
Clinical & Experimental Immunology, 1991academic.oup.com
Experimental autoimmune glomerulonephritis (EAG) was induced in brown Norway (BN)
rats by a single im 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 …
Summary
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.
Oxford University Press