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. 1994 Feb;81(2):317–321.

Reduction of spontaneous autoimmune diabetes in diabetes-prone BB rats with the novel immunosuppressant fusidic acid. Effect on T-cell proliferation and production of interferon-gamma.

F Nicoletti 1, R Di Marco 1, S Morrone 1, P Zaccone 1, D Lembo 1, S Grasso 1, A Santoni 1, P L Meroni 1, K Bendtzen 1
PMCID: PMC1422331  PMID: 8157281

Abstract

Diabetes-prone (DP) BB rats spontaneously develop a hyperglycaemic condition which closely resembles human insulin-dependent diabetes mellitus (IDDM), both in terms of clinical and histological features. The incidence of IDDM was significantly reduced when these animals were treated with 2 or 4 mg fusidic acid (FA)/day i.m. from day 30 to day 120 of age. In addition, the mean insulitis score was significantly diminished in the animals treated with FA compared to both vehicle-treated and untreated controls. Finally, 2 mg/day of FA i.m. prevented cell proliferation and interferon-gamma secretion from peripheral blood mononuclear cells upon ex vivo stimulation with concanavalin A. The capacity of FA to substantially reduce the incidence of autoimmune diabetes in a well-known animal model of human IDDM supports previous observations regarding the immunosuppressive properties of FA and its potential use in the treatment of human autoimmune diabetes.

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Selected References

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

  1. Bendtzen K., Diamant M., Faber V. Fusidic acid, an immunosuppressive drug with functions similar to cyclosporin A. Cytokine. 1990 Nov;2(6):423–429. doi: 10.1016/1043-4666(90)90051-t. [DOI] [PubMed] [Google Scholar]
  2. Bendtzen K., Diamant M., Horn T., Pedersen C., Buschard K. Effect of fusidic acid on interleukin-1 (IL-1)- and IL-6-induced pancreatic beta-cell functions in rats. J Endocrinol. 1992 Mar;132(3):345–352. doi: 10.1677/joe.0.1320345. [DOI] [PubMed] [Google Scholar]
  3. Bendtzen K. Immune hormones (cytokines); pathogenic role in autoimmune rheumatic and endocrine diseases. Autoimmunity. 1989;2(2):177–189. doi: 10.3109/08916938909019954. [DOI] [PubMed] [Google Scholar]
  4. Bendtzen K., Vesti-Nielsen N., Petersen J., Andersen V., Bendixen G. Treatment of chronic endogenous uveitis with fusidic acid. Lancet. 1991 Mar 2;337(8740):552–553. doi: 10.1016/0140-6736(91)91337-t. [DOI] [PubMed] [Google Scholar]
  5. Brynskov J., Freund L., Rasmussen S. N., Lauritsen K., de Muckadell O. S., Williams N., MacDonald A. S., Tanton R., Molina F., Campanini M. C. A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease. N Engl J Med. 1989 Sep 28;321(13):845–850. doi: 10.1056/NEJM198909283211301. [DOI] [PubMed] [Google Scholar]
  6. Buschard K., Pedersen C., Hansen S. V., Hageman I., Aaen K., Bendtzen K. Anti-diabetogenic effect of fusidic acid in diabetes prone BB rats. Autoimmunity. 1992;14(2):101–104. doi: 10.3109/08916939209083127. [DOI] [PubMed] [Google Scholar]
  7. Campbell I. L., Harrison L. C. A new view of the beta cell as an antigen-presenting cell and immunogenic target. J Autoimmun. 1990 Apr;3 (Suppl 1):53–62. doi: 10.1016/s0896-8411(09)90010-5. [DOI] [PubMed] [Google Scholar]
  8. Campbell I. L., Kay T. W., Oxbrow L., Harrison L. C. Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. J Clin Invest. 1991 Feb;87(2):739–742. doi: 10.1172/JCI115055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dean B. M., Walker R., Bone A. J., Baird J. D., Cooke A. Pre-diabetes in the spontaneously diabetic BB/E rat: lymphocyte subpopulations in the pancreatic infiltrate and expression of rat MHC class II molecules in endocrine cells. Diabetologia. 1985 Jul;28(7):464–466. doi: 10.1007/BF00280892. [DOI] [PubMed] [Google Scholar]
  10. Fathman C. G., Myers B. D. Cyclosporine therapy for autoimmune disease. N Engl J Med. 1992 Jun 18;326(25):1693–1695. doi: 10.1056/NEJM199206183262509. [DOI] [PubMed] [Google Scholar]
  11. Feutren G., Mihatsch M. J. Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. International Kidney Biopsy Registry of Cyclosporine in Autoimmune Diseases. N Engl J Med. 1992 Jun 18;326(25):1654–1660. doi: 10.1056/NEJM199206183262502. [DOI] [PubMed] [Google Scholar]
  12. Feutren G., Papoz L., Assan R., Vialettes B., Karsenty G., Vexiau P., Du Rostu H., Rodier M., Sirmai J., Lallemand A. Cyclosporin increases the rate and length of remissions in insulin-dependent diabetes of recent onset. Results of a multicentre double-blind trial. Lancet. 1986 Jul 19;2(8499):119–124. doi: 10.1016/s0140-6736(86)91943-4. [DOI] [PubMed] [Google Scholar]
  13. Frickhofen N., Kaltwasser J. P., Schrezenmeier H., Raghavachar A., Vogt H. G., Herrmann F., Freund M., Meusers P., Salama A., Heimpel H. Treatment of aplastic anemia with antilymphocyte globulin and methylprednisolone with or without cyclosporine. The German Aplastic Anemia Study Group. N Engl J Med. 1991 May 9;324(19):1297–1304. doi: 10.1056/NEJM199105093241901. [DOI] [PubMed] [Google Scholar]
  14. Hahn H. J., Lucke S., Klöting I., Volk H. D., Baehr R. V., Diamantstein T. Curing BB rats of freshly manifested diabetes by short-term treatment with a combination of a monoclonal anti-interleukin 2 receptor antibody and a subtherapeutic dose of cyclosporin A. Eur J Immunol. 1987 Jul;17(7):1075–1078. doi: 10.1002/eji.1830170728. [DOI] [PubMed] [Google Scholar]
  15. Langholz E., Brynskov J., Bendtzen K., Vilien M., Binder V. Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin. Aliment Pharmacol Ther. 1992 Aug;6(4):495–502. doi: 10.1111/j.1365-2036.1992.tb00563.x. [DOI] [PubMed] [Google Scholar]
  16. Langholz E., Brynskov J., Freund L. G., Bendtzen K. Fusidic acid for Behçet's colitis: a novel approach to T-cell specific immunosuppressive therapy. Dan Med Bull. 1991 Jun;38(3):284–284. [PubMed] [Google Scholar]
  17. Laupacis A., Stiller C. R., Gardell C., Keown P., Dupre J., Wallace A. C., Thibert P. Cyclosporin prevents diabetes in BB Wistar rats. Lancet. 1983 Jan 1;1(8314-5):10–12. doi: 10.1016/s0140-6736(83)91558-1. [DOI] [PubMed] [Google Scholar]
  18. Lichtiger S., Present D. H. Preliminary report: cyclosporin in treatment of severe active ulcerative colitis. Lancet. 1990 Jul 7;336(8706):16–19. doi: 10.1016/0140-6736(90)91521-b. [DOI] [PubMed] [Google Scholar]
  19. Macleod A. M., Thomson A. W. FK 506: an immunosuppressant for the 1990s? Lancet. 1991 Jan 5;337(8732):25–27. doi: 10.1016/0140-6736(91)93341-6. [DOI] [PubMed] [Google Scholar]
  20. Masuda K., Nakajima A., Urayama A., Nakae K., Kogure M., Inaba G. Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behçet's disease. Lancet. 1989 May 20;1(8647):1093–1096. doi: 10.1016/s0140-6736(89)92381-7. [DOI] [PubMed] [Google Scholar]
  21. Mordes J. P., Desemone J., Rossini A. A. The BB rat. Diabetes Metab Rev. 1987 Jul;3(3):725–750. doi: 10.1002/dmr.5610030307. [DOI] [PubMed] [Google Scholar]
  22. Nicoletti F., Meroni P. L., Barcellini W., Grasso S., Borghi M. O., Lunetta M., Di Marco R., Stefani S., Mughini L. FK-506 prevents diabetes in diabetes-prone BB/Wor rats. Int J Immunopharmacol. 1991;13(7):1027–1030. doi: 10.1016/0192-0561(91)90057-e. [DOI] [PubMed] [Google Scholar]
  23. Nicoletti F., Meroni P. L., Landolfo S., Gariglio M., Guzzardi S., Barcellini W., Lunetta M., Mughini L., Zanussi C. Prevention of diabetes in BB/Wor rats treated with monoclonal antibodies to interferon-gamma. Lancet. 1990 Aug 4;336(8710):319–319. doi: 10.1016/0140-6736(90)91860-d. [DOI] [PubMed] [Google Scholar]
  24. Nicoletti F., Meroni P. L., Lunetta M., Vigo R., Palermo T., Papalia D., Barcellini W., Di Mauro M., Caruso-Nicoletti M., Mughini L. Sodium fusidate and increased remission rate of insulin-dependent diabetes mellitus. Lancet. 1991 May 25;337(8752):1292–1292. doi: 10.1016/0140-6736(91)92964-4. [DOI] [PubMed] [Google Scholar]
  25. Nussenblatt R. B., Palestine A. G., Rook A. H., Scher I., Wacker W. B., Gery I. Treatment of intraocular inflammatory disease with cyclosporin A. Lancet. 1983 Jul 30;2(8344):235–238. doi: 10.1016/s0140-6736(83)90230-1. [DOI] [PubMed] [Google Scholar]
  26. Oschilewski U., Kiesel U., Kolb H. Administration of silica prevents diabetes in BB-rats. Diabetes. 1985 Feb;34(2):197–199. doi: 10.2337/diab.34.2.197. [DOI] [PubMed] [Google Scholar]
  27. Prud'homme G. J., Fuks A., Colle E., Seemayer T. A., Guttmann R. D. Immune dysfunction in diabetes-prone BB rats. Interleukin 2 production and other mitogen-induced responses are suppressed by activated macrophages. J Exp Med. 1984 Feb 1;159(2):463–478. doi: 10.1084/jem.159.2.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rostoker G., Toro L., Ben Maadi A., Ryckelynk J., Sadreux T., Rivalan J., Chevet D., Janin C., Lang P., Weil B. Cyclosporin in idiopathic steroid-resistant membranous glomerulonephritis. Lancet. 1989 Oct 21;2(8669):975–976. doi: 10.1016/s0140-6736(89)90979-3. [DOI] [PubMed] [Google Scholar]
  29. Stiller C. R., Dupré J., Gent M., Jenner M. R., Keown P. A., Laupacis A., Martell R., Rodger N. W., von Graffenried B., Wolfe B. M. Effects of cyclosporine immunosuppression in insulin-dependent diabetes mellitus of recent onset. Science. 1984 Mar 30;223(4643):1362–1367. doi: 10.1126/science.6367043. [DOI] [PubMed] [Google Scholar]
  30. Thomson A. W. The spectrum of action of new immunosuppressive drugs. Clin Exp Immunol. 1992 Aug;89(2):170–173. doi: 10.1111/j.1365-2249.1992.tb06927.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thomson A. W., Webster L. M. The influence of cyclosporin A on cell-mediated immunity. Clin Exp Immunol. 1988 Mar;71(3):369–376. [PMC free article] [PubMed] [Google Scholar]
  32. Tugwell P., Bombardier C., Gent M., Bennett K. J., Bensen W. G., Carette S., Chalmers A., Esdaile J. M., Klinkhoff A. V., Kraag G. R. Low-dose cyclosporin versus placebo in patients with rheumatoid arthritis. Lancet. 1990 May 5;335(8697):1051–1055. doi: 10.1016/0140-6736(90)92630-z. [DOI] [PubMed] [Google Scholar]
  33. Wick G., Müller P. U., Schwarz S. Effect of cyclosporin A on spontaneous autoimmune thyroiditis of Obese strain (OS) chickens. Eur J Immunol. 1982 Oct;12(10):877–881. doi: 10.1002/eji.1830121014. [DOI] [PubMed] [Google Scholar]
  34. Wiesner R. H., Ludwig J., Lindor K. D., Jorgensen R. A., Baldus W. P., Homburger H. A., Dickson E. R. A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis. N Engl J Med. 1990 May 17;322(20):1419–1424. doi: 10.1056/NEJM199005173222003. [DOI] [PubMed] [Google Scholar]

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