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Clin Exp Immunol. Sep 1990; 81(3): 446–453.
PMCID: PMC1534978

Therapeutic effect of 15-deoxyspergualin on the progression of lupus nephritis in MRL mice. I. Immunopathological analyses.

Abstract

The effect of 15-deoxyspergualin (DSP), a newly developed immunosuppressive agent, on the development of spontaneously occurring lupus glomerulonephritis in MRL-lpr mice was examined. Administration of the drug was initiated at the age of 13 or 17 weeks, when polyclonal B cell activation and lupus nephropathy were apparent or became prominent. Treatment with DSP for up to 19 weeks of age at a dose of 2 mg/kg twice a day or 5 mg/kg daily strongly suppressed the increment of IgG-producing cell numbers in the spleen and serum levels of immune complexes and anti-DNA antibodies. Glomerular histological score estimated by light microscopy and IgG and C3 deposition in renal glomeruli were improved, compared with untreated control mice. Thus, DSP was shown to suppress the progression of polyclonal B cell activation and lupus nephropathy in MRL/lpr mice. These results suggest that DSP may be used as a therapeutic agent for systemic lupus erythematosus.

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Selected References

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  • Adelman NE, Watling DL, McDevitt HO. Treatment of (NZB x NZW)F1 disease with anti-I-A monoclonal antibodies. J Exp Med. 1983 Oct 1;158(4):1350–1355. [PMC free article] [PubMed]
  • Alexander EL, Moyer C, Travlos GS, Roths JB, Murphy ED. Two histopathologic types of inflammatory vascular disease in MRL/Mp autoimmune mice. Model for human vasculitis in connective tissue disease. Arthritis Rheum. 1985 Oct;28(10):1146–1155. [PubMed]
  • Andrews BS, Eisenberg RA, Theofilopoulos AN, Izui S, Wilson CB, McConahey PJ, Murphy ED, Roths JB, Dixon FJ. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978 Nov 1;148(5):1198–1215. [PMC free article] [PubMed]
  • Austin HA, 3rd, Klippel JH, Balow JE, le Riche NG, Steinberg AD, Plotz PH, Decker JL. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986 Mar 6;314(10):614–619. [PubMed]
  • Berden JH, Hang L, McConahey PJ, Dixon FJ. Analysis of vascular lesions in murine SLE. I. Association with serologic abnormalities. J Immunol. 1983 Apr;130(4):1699–1705. [PubMed]
  • 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. [PubMed]
  • Carteron NL, Schimenti CL, Wofsy D. Treatment of murine lupus with F(ab')2 fragments of monoclonal antibody to L3T4. Suppression of autoimmunity does not depend on T helper cell depletion. J Immunol. 1989 Mar 1;142(5):1470–1475. [PubMed]
  • Casey TP. Systemic lupus erythematosus in NZB x NZW hybrid mice treated with the corticosteroid drug betamethasone. J Lab Clin Med. 1968 Mar;71(3):390–399. [PubMed]
  • Gronowicz E, Coutinho A, Melchers F. A plaque assay for all cells secreting Ig of a given type or class. Eur J Immunol. 1976 Aug;6(8):588–590. [PubMed]
  • Hahn BH, Bagby MK, Hamilton TR, Osterland CK. Comparison of therapeutic and immunosuppressive effects of azathioprine, prednisolone and combined therapy in NZP-NZW mice. Arthritis Rheum. 1973 Mar-Apr;16(2):163–170. [PubMed]
  • Howie JB, Helyer BJ. The immunology and pathology of NZB mice. Adv Immunol. 1968;9:215–266. [PubMed]
  • Kolb WP, Kolb LM, Podack ER. C1q: isolation from human serum in high yield by affinity chromatography and development of a highly sensitive hemolytic assay. J Immunol. 1979 May;122(5):2103–2111. [PubMed]
  • Makino M, Fujiwara M, Watanabe H. Studies on the mechanisms of the development of lupus nephritis in BXSB mice. I. Analyses of immunological abnormalities at the onset period. J Clin Lab Immunol. 1987 Mar;22(3):127–131. [PubMed]
  • Makino M, Fujiwara M, Watanabe H. Studies on the mechanisms of the development of lupus nephritis in BXSB mice. II. Comparative studies between male BXSB and MRL/lpr mice at the onset period. J Clin Lab Immunol. 1988 Feb;25(2):83–88. [PubMed]
  • Makino M, Morita T, Fujiwara M. Histopathological characteristics of the kidney in recombinant inbred mice established from MRL/lpr x AKR crossing. Dissociation of severity of lupus nephritis from the degree of lymphadenopathy. Virchows Arch B Cell Pathol Incl Mol Pathol. 1988;56(1):59–65. [PubMed]
  • Makino M, Fujiwara M, Aoyagi T, Umezawa H. Immunosuppressive activities of deoxyspergualin. I. Effect of the long-term administration of the drug on the development of murine lupus. Immunopharmacology. 1987 Oct-Nov;14(2):107–113. [PubMed]
  • Makino M, Fujiwara M, Watanabe H, Aoyagi T, Umezawa H. Immunosuppressive activities of deoxyspergualin. II. The effect on the antibody responses. Immunopharmacology. 1987 Oct-Nov;14(2):115–121. [PubMed]
  • Makino M, Fujiwara M, Watanabe H, Sugano H, Arakawa M. Evaluation of different preparations of aggregated human IgG for use as a standard in the assays of circulating immune complexes. J Clin Lab Immunol. 1986 Nov;21(3):151–157. [PubMed]
  • Masuda T, Mizutani S, Iijima M, Odai H, Suda H, Ishizuka M, Takeuchi T, Umezawa H. Immunosuppressive activity of 15-deoxyspergualin and its effect on skin allografts in rats. J Antibiot (Tokyo) 1987 Nov;40(11):1612–1618. [PubMed]
  • Morrow WJ, Youinou P, Isenberg DA, Snaith ML. Systemic lupus erythematosus: 25 years of treatment related to immunopathology. Lancet. 1983 Jul 23;2(8343):206–210. [PubMed]
  • Moyer CF, Strandberg JD, Reinisch CL. Systemic mononuclear-cell vasculitis in MRL/Mp-lpr/lpr mice. A histologic and immunocytochemical analysis. Am J Pathol. 1987 May;127(2):229–242. [PMC free article] [PubMed]
  • Nemoto K, Abe F, Nakamura T, Ishizuka M, Takeuchi T, Umezawa H. Blastogenic responses and the release of interleukins 1 and 2 by spleen cells obtained from rat skin allograft recipients administered with 15-deoxyspergualin. J Antibiot (Tokyo) 1987 Jul;40(7):1062–1064. [PubMed]
  • Okubo M, Inoue K, Umetani N, Sato N, Kamata K, Masaki Y, Uchiyama T, Yan XJ, Aoyagi T, Shirai T. Lupus nephropathy in New Zealand F1 hybrid mice treated by (-)15-deoxyspergualin. Kidney Int. 1988 Oct;34(4):467–473. [PubMed]
  • Okudaira H, Ogita T, Miyamoto T, Shiga J, Suko M, Okudaira K, Terada E, Ghoda A, Terada K, Saito M, et al. Interstitial pneumonitis in autoimmune MRL/lpr mice and its treatment with cyclosporin A. Clin Immunol Immunopathol. 1986 Jan;38(1):47–54. [PubMed]
  • Santoro TJ, Portanova JP, Kotzin BL. The contribution of L3T4+ T cells to lymphoproliferation and autoantibody production in MRL-lpr/lpr mice. J Exp Med. 1988 May 1;167(5):1713–1718. [PMC free article] [PubMed]
  • Shiraki M, Fujiwara M, Tomura S. Long term administration of cyclophosphamide in MRL/1 mice. I. The effects on the development of immunological abnormalities and lupus nephritis. Clin Exp Immunol. 1984 Feb;55(2):333–339. [PMC free article] [PubMed]
  • Smith HR, Chused TM, Steinberg AD. Cyclophosphamide-induced changes in the MRL-lpr/lpr mouse: effects upon cellular composition, immune function, and disease. Clin Immunol Immunopathol. 1984 Jan;30(1):51–61. [PubMed]
  • 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. [PubMed]
  • Takeuchi T, Iinuma H, Kunimoto S, Masuda T, Ishizuka M, Takeuchi M, Hamada M, Naganawa H, Kondo S, Umezawa H. A new antitumor antibiotic, spergualin: isolation and antitumor activity. J Antibiot (Tokyo) 1981 Dec;34(12):1619–1621. [PubMed]
  • Talal N, Steinberg AD. The pathogenesis of autoimmunity in New Zealand black mice. Curr Top Microbiol Immunol. 1974;64(0):79–103. [PubMed]
  • Tarkowski A, Jonsson R, Sanchez R, Klareskog L, Koopman WJ. Features of renal vasculitis in autoimmune MRL lpr/lpr mice: phenotypes and functional properties of infiltrating cells. Clin Exp Immunol. 1988 Apr;72(1):91–97. [PMC free article] [PubMed]
  • Umezawa H, Ishizuka M, Takeuchi T, Abe F, Nemoto K, Shibuya K, Nakamura T. Suppression of tissue graft rejection by spergualin. J Antibiot (Tokyo) 1985 Feb;38(2):283–284. [PubMed]

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