Single and multiple drug therapy in autologous immune complex nephritis in rats.
Autologous immune complex (AIC) nephritis is a form of chronic renal disease with remarkable similarities to idiopathic membranous nephropathy occurring in man. AIC nephritis was induced in 160 gram Lewis rats with a single footpad injection of tubular brush-border antigen (FxIA) in complete Freund's adjuvant. When killed at 8 weeks, 85 per cent of the rats demonstrated typical diffuse glomerular deposits of immunoglobulin G and B1C (C1/3 component of complement) by immunofluorescent microscopy, and subepithelial electron-dense deposits by electron microscopy. Both immune complex disease and significant proteinuria occurred in two-thirds of these animals. An attempt to modify the natural course of established AIC nephritis using large doses of potent glucocorticoids (methyl-prednisolone), anti-inflammatory agents (acetylsalicylic acid, indomethacin, and cyproheptadine), and immunosuppressive drugs (cyclophosphamide, azathioprine) was begun 4 weeks after initial immunization and continued for 4 more weeks. None of the single drug nor multiple drug protocols employed was of demonstrable benefit in ameliorating the immune events operating in AIC nephritis. Cyclophosphamide and indomethacin, when used singly, were associated with significant mortality in the animals studied. All combined drug protocols involving glucocorticoids and antimetabolites were associated with unacceptable mortality as well. Of interest, immune complexes could not be demonstrated in the vascular choroid plexus of any rat with AIC nephritis. This failure to modify the course of established renal disease (AIC) in an experimental animal with generally available pharmacologic agents, is similar to the usual results of such treatment in chronic renal disease (idiopathic membranous nephropathy) in man. It is possible that new and more potent anti-inflammatory agents employed singly or in various combinations, will permit more successful manipulation of the host's immunologic system to prevent or modify immune injury of the renal glomerulus.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D001485:Basement Membrane / Q000473:pathology; D003176:Complement C3; D003520:Cyclophosphamide / Q000627:therapeutic use; D003533:Cyproheptadine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology; D007105:Immune Complex Diseases / Q000188:drug therapy*; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D011507:Proteinuria; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003176:Complement C3; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D003533:Cyproheptadine; D003520:Cyclophosphamide; D001379:Azathioprine; D001241:Aspirin; D008775:Methylprednisolone; D007213:Indomethacin