Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1983 Jun;52(3):586–594.

Cyclosporin A inhibits acute serum sickness nephritis in rabbits.

G H Neild, K Ivory, M Hiramatsu, D G Williams
PMCID: PMC1536029  PMID: 6347471

Abstract

The effect of the immunosuppressive agent cyclosporin A (Cy A) on the renal injury in acute serum sickness was examined in rabbits. Serum sickness was induced in 23 untreated NZW rabbits by a single intravenous injection of bovine serum albumin (BSA) 250 mg/kg with E. coli endotoxin (5 micrograms/kg): BSA was eliminated after 8.6 +/- 0.16 days (mean +/- s.e. (mean]; proteinuria occurred in 19 (84%) and glomerular proliferation in 20 (87%) rabbits. When Cy A (15 or 25 mg/kg) was given daily by intramuscular injection, starting either 2 days before or at the time of induction of acute serum sickness, proteinuria was profoundly reduced and glomerular proliferation was inhibited. Even when rabbits were first treated with Cy A (25 mg/kg) 5 days after the induction of disease proteinuria and glomerular proliferation were similarly inhibited. When the treated animals were compared with controls there were no differences in the following: time to elimination of BSA, amount or size of circulating immune complexes, fall in serum C3 at immune elimination, or deposition of immune reactants in the glomeruli. These results show that Cy A inhibits the renal injury of acute serum sickness and indicate that T cells may play a role in mediating the nephritis in this condition.

Full text

PDF
586

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Borel J. F., Feurer C., Magnée C., Stähelin H. Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology. 1977 Jun;32(6):1017–1025. [PMC free article] [PubMed] [Google Scholar]
  2. Bunjes D., Hardt C., Röllinghoff M., Wagner H. Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2. Eur J Immunol. 1981 Aug;11(8):657–661. doi: 10.1002/eji.1830110812. [DOI] [PubMed] [Google Scholar]
  3. DIXON F. J., VAZQUEZ J. J., WEIGLE W. O., COCHRANE C. G. Pathogenesis of serum sickness. AMA Arch Pathol. 1958 Jan;65(1):18–28. [PubMed] [Google Scholar]
  4. Gratwohl A., Forster I., Speck B. Skin grafts in rabbits with cyclosporin A: absence of induction of tolerance and untoward side effects. Transplantation. 1981 Feb;31(2):136–138. doi: 10.1097/00007890-198102000-00011. [DOI] [PubMed] [Google Scholar]
  5. Green C. J., Allison A. C., Precious S. Induction of specific tolerance in rabbits by kidney allografting and short periods of cyclosporin-A treatment. Lancet. 1979 Jul 21;2(8134):123–125. doi: 10.1016/s0140-6736(79)90005-9. [DOI] [PubMed] [Google Scholar]
  6. Holdsworth S. R., Neale T. J., Wilson C. B. Abrogation of macrophage-dependent injury in experimental glomerulonephritis in the rabbit. Use of an antimacrophage serum. J Clin Invest. 1981 Sep;68(3):686–698. doi: 10.1172/JCI110304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hunsicker L. G., Shearer T. P., Plattner S. B., Weisenburger D. The role of monocytes in serum sickness nephritis. J Exp Med. 1979 Sep 19;150(3):413–425. doi: 10.1084/jem.150.3.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. KNIKER W. T., COCHRANE C. G. PATHOGENIC FACTORS IN VASULAR LESIONS OF EXPERIMENTAL SERUM SICKNESS. J Exp Med. 1965 Jul 1;122:83–98. doi: 10.1084/jem.122.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Larsson E. L. Cyclosporin A and dexamethasone suppress T cell responses by selectively acting at distinct sites of the triggering process. J Immunol. 1980 Jun;124(6):2828–2833. [PubMed] [Google Scholar]
  10. Morris P. J. Cyclosporin A. Transplantation. 1981 Nov;32(5):349–354. [PubMed] [Google Scholar]
  11. Neild G. H., Ivory K., Williams D. G. Effects of high-dose i.v. steroid (pulse) therapy on acute serum sickness in rabbits. Br J Exp Pathol. 1982 Dec;63(6):606–614. [PMC free article] [PubMed] [Google Scholar]
  12. Nussenblatt R. B., Rodrigues M. M., Wacker W. B., Cevario S. J., Salinas-Carmona M. C., Gery I. Cyclosporin a. Inhibition of experimental autoimmune uveitis in Lewis rats. J Clin Invest. 1981 Apr;67(4):1228–1231. doi: 10.1172/JCI110138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Parks D. E., Weigle W. O. Current perspectives on the cellular mechanisms of immunologic tolerance. Clin Exp Immunol. 1980 Feb;39(2):257–262. [PMC free article] [PubMed] [Google Scholar]
  14. Ragsdale C. G., Arend W. P. Neutral protease secretion by human monocytes. Effect of surface-bound immune complexes. J Exp Med. 1979 Apr 1;149(4):954–968. doi: 10.1084/jem.149.4.954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Schwartz B. S., Edgington T. S. Immune complex-induced human monocyte procoagulant activity. I. a rapid unidirectional lymphocyte-instructed pathway. J Exp Med. 1981 Sep 1;154(3):892–906. doi: 10.1084/jem.154.3.892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shulman H., Striker G., Deeg H. J., Kennedy M., Storb R., Thomas E. D. Nephrotoxicity of cyclosporin A after allogeneic marrow transplantation: glomerular thromboses and tubular injury. N Engl J Med. 1981 Dec 3;305(23):1392–1395. doi: 10.1056/NEJM198112033052306. [DOI] [PubMed] [Google Scholar]
  17. Tanaka J., Yata J. Immune complex-dependent T cell-mediated cytostasis (IDTC). Clin Exp Immunol. 1981 Jul;45(1):215–223. [PMC free article] [PubMed] [Google Scholar]
  18. White D. J., Plumb A. M., Pawelec G., Brons G. Cyclosporin A: an immunosuppressive agent preferentially active against proliferating T cells. Transplantation. 1979 Jan;27(1):55–58. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES