title: The effect of cyclosporin A on the interstitial mononuclear cell infiltration and the induction of Heymann's nephritis.
abstract: Heymann's nephritis was induced with brush-border (BB) antigen. Interstitial mononuclear cell infiltration was studied with cytological examinations of fine-needle aspiration biopsies (FNAB), and with immunoperoxidase stains of frozen sections with monoclonal antisera. The effect of cyclosporin A (CyA), 20 mg/kg when administered intraperitoneally for 8 days in association with both initial immunization, and with the booster 4 weeks later, on the interstitial leukocyte infiltration and on the development of membranous glomerulonephritis (MGN) and proteinuria were investigated. Another group of rats was immunized, but not given CyA. Experimental animals were killed in groups 3, 6 and 20 weeks after initial immunization. CyA inhibited significantly the initial interstitial lymphocyte and blast cell response at 3 weeks (FNAB), but did not inhibit the secondary response after the booster. The anti-BB titre reacted in a similar fashion. Immunoperoxidase stains indicated a clearly suppressed T suppressor/cytolytic (T s/c) cell response. Glomerular basement membrane (GBM) deposits of IgG developed more slowly and were more scarce in the CyA-treated rats, when compared with the untreated group. Only one out of 15 CyA treated rats developed C3 deposits in the GBM during the course of the study, and none developed proteinuria, when most untreated rats (10/17) had C3 deposits and were nephrotic at 20 weeks. Thus, CyA depressed the initial interstitial cellular response after immunization with BB antigen, and also inhibited the development of antibody response, C3 deposits and proteinuria of Heymann nephritis. These effects of CyA may be contributed to an inhibited amplification of the autoimmune response associated with interstitial damage and continuous release of autoantigen.
authors.affiliation: Minerva Institute for Medical Research, Fourth Department of Medicine, University of Helsinki, Finland.
authors.forename: C
authors.initials: C
authors.lastname: Grönhagen-Riska
authors.forename: E
authors.initials: E
authors.lastname: von Willebrand
authors.forename: T
authors.initials: T
authors.lastname: Tikkanen
authors.forename: E
authors.initials: E
authors.lastname: Honkanen
authors.forename: A
authors.initials: A
authors.lastname: Miettinen
authors.forename: H
authors.initials: H
authors.lastname: Holthöfer
authors.forename: T
authors.initials: T
authors.lastname: Törnroth
mesh_terms: D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology*; D015433:Glomerulonephritis, Membranous / Q000517:prevention & control; D007672:Kidney Cortex / Q000276:immunology*; D007958:Leukocyte Count / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D003524:Cyclosporins