Effects of cyclosporin A on the development of immune-mediated interstitial nephritis.
We examined the effect of daily cyclosporin A administration on the development and extent of tubulointerstitial nephritis produced in rats immunized with tubular basement membranes in adjuvant. Six mg/kg/day of cyclosporin A, given from the time of immunization, completely blocked the development of interstitial lesions and renal insufficiency. The administration of cyclosporin A after the development of interstitial nephritis also arrested the progression of the histological lesions. Both T cell-mediated and humoral immunity were markedly reduced by the administration of cyclosporin A, as evidenced by the near absence of delayed-type hypersensitivity responses and by the reduced production of anti-tubular basement membrane antibodies. Cell admixture experiments indicated that impairment of the delayed-type hypersensitivity response to tubular antigen was probably not the result of active suppression, and suggested that the protective effect of cyclosporin A might be secondary to its direct inhibitory action on the activation of nephritogenic T and B cells. Finally, the treatment of control rats with cyclosporin A, in the doses used, did not produce any detectable kidney damage nor did it impair renal function. We conclude that cyclosporin A can be an effective prophylactic and therapeutic agent in autoimmune interstitial nephritis in rats.
Shih
W
W
Department of Medicine, University of Pennsylvania, Philadelphia.
Hines
W H
WH
Neilson
E G
EG
D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control; D001402:B-Lymphocytes / Q000276:immunology; D003524:Cyclosporins / Q000627:therapeutic use*; D005620:Freund's Adjuvant; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007116:Immunization, Passive; D007684:Kidney Tubules; D009395:Nephritis, Interstitial / Q000276:immunology* / Q000517:prevention & control; D011817:Rabbits; D051381:Rats; D011914:Rats, Inbred BN; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D003524:Cyclosporins; C035812:renal tubular antigen; D005620:Freund's Adjuvant