Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Aug;89(2):179–184. doi: 10.1111/j.1365-2249.1992.tb06929.x

The effects of CP 17193, an immunosuppressive pyrazaloquinoline, on the development of spontaneous lupus disease in NZBW F1 hybrid mice.

R V Bundick 1, R P Eady 1
PMCID: PMC1554431  PMID: 1638762

Abstract

The effects of the immunosuppressive agent CP 17193 on the development of spontaneous lupus disease in female NZBW F1 hybrid mice were investigated. Long term dosing with CP 17193 markedly delayed the onset of mortality but did not extend the long term survival of the mice. CP 17193 significantly inhibited immune complex deposition in the glomeruli of 30- and 35-week-old mice and also reduced the levels of proteinuria in the 35-week-old mice. There was a slight reduction in the levels of circulating antinuclear antibody to ds DNA in CP 17193-treated mice but this was not statistically significant. Studies on immune cell function of 35-week-old mice dosed with CP 17193 showed significant reduction in the total numbers of spontaneous polyclonal antibody producing cells. Analysis of the results revealed these effects to result from a marked reduction in total spleen cell numbers in CP 17193-treated mice. When results were expressed as activity per cell unit the differences between drug-treated and control mice were small. Spleen cells from mice given a shorter dosing schedule of 7 weeks with CP 17193 showed an augmentation of IL-2 production and responsiveness. These results show CP 17193 having interesting selective immunomodulating activity on the immunopathogenesis of spontaneous murine lupus disease. Furthermore, compounds with this profile of activity may have a potential role in the treatment of some autoimmune diseases.

Full text

PDF
179

Selected References

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

  1. Altman A., Theofilopoulos A. N., Weiner R., Katz D. H., Dixon F. J. Analysis of T cell function in autoimmune murine strains. Defects in production and responsiveness to interleukin 2. J Exp Med. 1981 Sep 1;154(3):791–808. doi: 10.1084/jem.154.3.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andrews B. S., Eisenberg R. A., Theofilopoulos A. N., Izui S., Wilson C. B., McConahey P. J., Murphy E. D., Roths J. B., Dixon F. J. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978 Nov 1;148(5):1198–1215. doi: 10.1084/jem.148.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cavallo T., Graves K., Granholm N. A. Murine lupus nephritis: effects of cyclophosphamide on circulating and tissue bound immunoreactants. Clin Exp Immunol. 1984 Jan;55(1):67–73. [PMC free article] [PubMed] [Google Scholar]
  4. Dauphinée M. J., Kipper S. B., Wofsy D., Talal N. Interleukin 2 deficiency is a common feature of autoimmune mice. J Immunol. 1981 Dec;127(6):2483–2487. [PubMed] [Google Scholar]
  5. Fauci A. S., Pratt K. R. Activation of human B lymphocytes. I. Direct plaque-forming cell assay for the measurement of polyclonal activation and antigenic stimulation of human B lymphocytes. J Exp Med. 1976 Sep 1;144(3):674–684. doi: 10.1084/jem.144.3.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fidler J. M., McDaniel E. M., Golub E. S. Regulation of the immune response. 3. Effect of the "accelerated" response on hapten-carrier responses. Cell Immunol. 1972 May;4(1):29–38. doi: 10.1016/0008-8749(72)90003-2. [DOI] [PubMed] [Google Scholar]
  7. Gabrielsen A. E., Olsen C. T. Dactinomycin treatment of murine lupus erythematosus. II. Dose and schedule of administration. Clin Immunol Immunopathol. 1980 Oct;17(2):257–263. doi: 10.1016/0090-1229(80)90094-x. [DOI] [PubMed] [Google Scholar]
  8. Gunn H. C., Ryffel B. Successful treatment of autoimmunity in (NZB X NZW)F1 mice with cyclosporin and (Nva2)-cyclosporin: II. Reduction of glomerulonephritis. Clin Exp Immunol. 1986 May;64(2):234–242. [PMC free article] [PubMed] [Google Scholar]
  9. Gunn H. C. Successful treatment of autoimmunity in (NZB X NZW)F1 mice with cyclosporin and (Nva2)-cyclosporin: I. Reduction of autoantibodies. Clin Exp Immunol. 1986 May;64(2):225–233. [PMC free article] [PubMed] [Google Scholar]
  10. Hahn B. H., Knotts L. L. Alteration of lymphocyte function in NZB/NZW mice. IV. Response to levamisole. Arthritis Rheum. 1979 Mar;22(3):236–242. doi: 10.1002/art.1780220305. [DOI] [PubMed] [Google Scholar]
  11. Hang L., Slack J. H., Amundson C., Izui S., Theofilopoulos A. N., Dixon F. J. Induction of murine autoimmune disease by chronic polyclonal B cell activation. J Exp Med. 1983 Mar 1;157(3):874–883. doi: 10.1084/jem.157.3.874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Henderson D. J., Naya I., Bundick R. V., Smith G. M., Schmidt J. A. Comparison of the effects of FK-506, cyclosporin A and rapamycin on IL-2 production. Immunology. 1991 Jul;73(3):316–321. [PMC free article] [PubMed] [Google Scholar]
  13. Ishizaka S., Tsujii T. IL-2 antibody production in lupus mice. Cell Immunol. 1989 Jan;118(1):100–107. doi: 10.1016/0008-8749(89)90360-2. [DOI] [PubMed] [Google Scholar]
  14. Israel-Biet D., Noel L. H., Bach M. A., Dardenne M., Bach J. F. Marked reduction of DNA antibody production and glomerulopathy in thymulin (FTS-Zn) or cyclosporin A treated (NZB X NZW) F1 mice. Clin Exp Immunol. 1983 Nov;54(2):359–365. [PMC free article] [PubMed] [Google Scholar]
  15. Jones M. G., Harris G. Prolongation of life in female NZB/NZW (F1) hybrid mice by cyclosporin A. Clin Exp Immunol. 1985 Jan;59(1):1–9. [PMC free article] [PubMed] [Google Scholar]
  16. Lombardino J. G., Otterness I. G. Novel immunosuppressive agents. Potent immunological activity of some bensothiopyrano [4,3-c]pyrazol-3-ones. J Med Chem. 1981 Jul;24(7):830–834. doi: 10.1021/jm00139a012. [DOI] [PubMed] [Google Scholar]
  17. Nakano T., Yamashita Y., Ohsugi Y., Sugawara Y., Hata S., Takagaki Y. The effect of CCA (Lobenzarit disodium) on the suppressor T cell function and the production of autoantibodies in New Zealand black and New Zealand white F1 mice. Immunopharmacology. 1983 Apr;5(4):293–302. doi: 10.1016/0162-3109(83)90045-0. [DOI] [PubMed] [Google Scholar]
  18. Ohsugi Y., Nakano T., Hata S. I., Niki R., Matsuno T., Nishii Y., Takagaki Y. N-(2-Carboxyphenyl)-4-chloroanthranilic acid disodium salt: prevention of autoimmune kidney disease in NZB/NZW F1 hybird mice. J Pharm Pharmacol. 1978 Feb;30(2):126–128. doi: 10.1111/j.2042-7158.1978.tb13180.x. [DOI] [PubMed] [Google Scholar]
  19. Otterness I. G., Bliven M. L. The mechanism of tumor allograft survival induced by CP-17,193. Immunopharmacology. 1982 Aug;4(4):341–354. doi: 10.1016/0162-3109(82)90055-8. [DOI] [PubMed] [Google Scholar]
  20. Otterness I. G. Comparative activity of CP-17,193 and five established immunosuppressives toward the antigens SRBC and EL4. Clin Exp Immunol. 1981 Nov;46(2):332–339. [PMC free article] [PubMed] [Google Scholar]
  21. Owen K. L., Shibata T., Izui S., Walker S. E. Recombinant interleukin-2 therapy of systemic lupus erythematosus in the New Zealand black/New Zealand white mouse. J Biol Response Mod. 1989 Aug;8(4):366–374. [PubMed] [Google Scholar]
  22. Sawada S., Suzuki G., Kawase Y., Takaku F. Novel immunosuppressive agent, FK506. In vitro effects on the cloned T cell activation. J Immunol. 1987 Sep 15;139(6):1797–1803. [PubMed] [Google Scholar]
  23. Steinberg A. D., Krakauer R., Reinertsen J. L., Klassen L. W., Ilfeld D., Reeves J. P., Williams G. W., Antonovych T. Therapeutic studies in NZB/NZW mice. VI. Age-dependent effects of concanavalin A stimulated spleen cell supernate. Arthritis Rheum. 1978 Mar;21(2):204–209. doi: 10.1002/art.1780210205. [DOI] [PubMed] [Google Scholar]
  24. Takabayashi K., Koike T., Kurasawa K., Matsumura R., Sato T., Tomioka H., Ito I., Yoshiki T., Yoshida S. Effect of FK-506, a novel immunosuppressive drug on murine systemic lupus erythematosus. Clin Immunol Immunopathol. 1989 Apr;51(1):110–117. doi: 10.1016/0090-1229(89)90211-0. [DOI] [PubMed] [Google Scholar]
  25. Tarkowski A., Gunnarsson K., Stålhandske T. Effects of LS-2616 administration upon the autoimmune disease of (NZB x NZW) F1 hybrid mice. Immunology. 1986 Dec;59(4):589–594. [PMC free article] [PubMed] [Google Scholar]
  26. Theofilopoulos A. N., Dixon F. J. Etiopathogenesis of murine SLE. Immunol Rev. 1981;55:179–216. doi: 10.1111/j.1600-065x.1981.tb00343.x. [DOI] [PubMed] [Google Scholar]
  27. Walker S. E., Anver M. R. Accelerated appearance of neoplasms in female NZB/NZW mice treated with high-dose cyclophosphamide. Arthritis Rheum. 1979 Dec;22(12):1338–1343. doi: 10.1002/art.1780221204. [DOI] [PubMed] [Google Scholar]
  28. Walker S. E., Solsky M., Schnitzer B. Prolonged lifespans in female NZB/NZW mice treated with the experimental immunoregulatory drug frentizole. Arthritis Rheum. 1982 Nov;25(11):1291–1297. doi: 10.1002/art.1780251104. [DOI] [PubMed] [Google Scholar]
  29. Wofsy D., Murphy E. D., Roths J. B., Dauphinée M. J., Kipper S. B., Talal N. Deficient interleukin 2 activity in MRL/Mp and C57BL/6J mice bearing the lpr gene. J Exp Med. 1981 Nov 1;154(5):1671–1680. doi: 10.1084/jem.154.5.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES