Effect of cyclosporine A on mercury-induced autoimmune glomerulonephritis in the Brown Norway rat.
To test the effect of cyclosporine A (CsA) in mercuric chloride (HgCl2)-induced nephritis in the Brown-Norway (BN) rat, we treated groups of intoxicated rats with varying doses of CsA for a period of 2 months. All manifestations of HgCl2-induced disease were prevented in rats treated concurrently with CsA at either 7 or 10 mg/kg/day. Partial suppression was evident at lower daily doses, but not with bi-weekly CsA administration. The initial phase of HgCl2-induced nephritis could be completely suppressed with a short, 15 day course of CsA. The later phase of the disease could be tempered by CsA administration starting on day 10 after the first HgCl2 injection. The optimal regimen of 7 mg/kg/day for 60 days was not associated with any evidence of CsA toxicity. CsA appears to interfere with the polyclonal activation of B cells observed in HgCl2-induced autoimmune disease, accounting for its striking preventive and curative effect in this model.
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000517:prevention & control*; D001835:Body Weight / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000032:analysis; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007677:Kidney Function Tests; D008628:Mercury / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats
D003524:Cyclosporins; D007073:Immunoglobulin E; D008628:Mercury