Abstract

We investigated the effects of cyclosporin A (CyA) on accelerated passive Heymann nephritis, an experimental model of membranous nephropathy, that is characterized by immune complex deposition on the glomerular basement membrane. The nephritis was induced in rats by injection of antiserum against the antigen located in the renal tubular brush border membrane and sensitization with rabbit gamma-globulin. CyA was administered p.o. at the dose of 2.5, 10 or 20 mg/kg/day for 40 days after the injection of the antiserum. The administration of CyA resulted in marked suppression of proteinuria and hypercholesterolemia in the nephritic rats. In light microscopy, nephritic control rats showed thickening of the glomerular basement membrane and spike formation in the glomeruli. CyA significantly reduced the appearance of the glomerular alteration. The production of antibody was dramatically attenuated by CyA administration. However, CyA did not decrease the number of circulating white blood cells and platelets below the normal level. In conclusion, CyA suppressed the progress of accelerated passive Heymann nephritis in a dose-dependent manner. The effect of CyA is likely attributable to the powerful depression of antibody production.

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