CYCLOPHOSPHAMIDE TREATMENT OF RENAL DISEASE IN (NZB &amp;times; NZW) F1 HYBRID MICE

Russell, Pamela J.; Hicks, John

doi:10.1016/s0140-6736(68)92778-5

Cited by 102 publications

(41 citation statements)

References 5 publications

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“…As they age, they develop, spontaneously and uniformly, autoantibodies with specificity to nucleic acid antigens (1), erythrocytes with a positive Coombs test (1,2), lymphocytes (3), and lethal immune-complex glomerulonephritis (4,5). The course of disease in NZB/NZW mice and in SLE can be modified with prolonged high-dose cyclophosphamide therapy which results in some suppression of anti-DNA antibodies and renal disease and prolongation of life (6)(7)(8)(9). Thoracic duct drainage, another mode of immunosuppression resulting in isolated lymphocyte depletion (cell-free lymph is reinfused after lymphocyte separation), has also been shown to be effective in decreasing the disease activity in SLE as well as in rheumatoid arthritis (10).…”

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confidence: 99%

Successful treatment of autoimmune disease in (NZB/NZW)F1 female mice by using fractionated total lymphoid irradiation.

Slavin¹

1979

Proc. Natl. Acad. Sci. U.S.A.

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confidence: 99%

Successful treatment of autoimmune disease in (NZB/NZW)F1 female mice by using fractionated total lymphoid irradiation.

Slavin¹

1979

Proc. Natl. Acad. Sci. U.S.A.

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“…These agents have included corticosteroids (1,2), azathioprine (3,4), cyclophosphamide (5,6) and anti-lymphocyte globulin (7,8).…”

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Comparison of therapeutic and immunosuppressive effects of azathioprine, prednisolone and combined therapy in nzp/nzw mice

Hahn

Bagby

Hamilton

et al. 1973

Arthritis & Rheumatism

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Since NZB/NZW mice develop an immune nephritis similar t o that of systemic lupus erythematosus in man, a study was designed in these mice to compare the clinical and immunologic effects of three immunosuppressive drug regimens. For 72 weeks, groups of 20 mice received daily oral therapy with a) no drugs, b) azathioprine, c) prednisolone or d) combined azathioprine-prednisolone. The combined regimen was superior t o either drug used alone in preventing deaths from renal disease. Prednisolone alone also prolonged life significantly, but not as effectively as combination therapy. Azathioprine alone was not effective. All drugs suppressed the antibody response to an exogenous antigen (Vi polysaccharide) equally well. None of the drug regimens prevented the appearance of proteinuria, antinuclear antibodies, Coombs' antibody, or 7-globulin deposits in glomeruli. However, the ability of a therapeutic regimen t o suppress antibodies to native DNA correlated well with its ability t o suppress renal disease. No malignancies were found among 73 animals autopsied, but significant hepatic damage occurred in the groups receiving prednisolone. Thus, combined therapy was superior t o either drug used alone, and the immunosuppressive effect of greatest clinical importance seemed to be the ability to prevent formation of anti-DNA antibodies.New Zealand black and New Zealand white hybrid mice (NZB/NZW F,) spontaneously develop a disease quite similar to systemic lupus erythematosus (SLE) in man. Virtually all mice of this strain develop lethal, immune complex

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“…In a detailed study Russell and Hicks (2) found a 140/, incidence of tumors in cyclophosphamidetreated mice, which is not much different from that found in the present study. However, the effectiveness of therapy far outweighed the risk of malignancy (2). Prolonged treatment by Hahn and coworkers (9) with azathioprine or azathioprine and prednisolone did not lead to malignancy.…”

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confidence: 99%

“…Female NZB/W mice are particularly useful because they regularly develop glomerulonephritis, from which they die, generally between 7 and 14 months of age. Several studies have demonstrated the efficacy of immunosuppressive drug therapy in retarding the progressive renal disease of NZB/W mice (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) …”

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Therapeutic studies in NZB/W MICE

Steinberg

Gelfand

Hardin

et al. 1975

Arthritis & Rheumatism

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Female NZB/W mice develop a disease closely resembling human systemic lupus and serve as an animal model for therapeutic studies. Several previous studies have demonstrated the efficacy of different immunosuppressive drug regimens in the therapy of glomerulonephritis in NZB/W mice. After the onset of immune complex deposition, treatment with intermittent high doses of cyclophosphamide or daily low doses of the combination of cyclophosphamide, azathioprine, and methylprednisolone has been effective. The present study was designed to compare such effective regimens in mice early in the course of their

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CYCLOPHOSPHAMIDE TREATMENT OF RENAL DISEASE IN (NZB × NZW) F1 HYBRID MICE

Cited by 102 publications

References 5 publications

Successful treatment of autoimmune disease in (NZB/NZW)F1 female mice by using fractionated total lymphoid irradiation.

Successful treatment of autoimmune disease in (NZB/NZW)F1 female mice by using fractionated total lymphoid irradiation.

Comparison of therapeutic and immunosuppressive effects of azathioprine, prednisolone and combined therapy in nzp/nzw mice

Therapeutic studies in NZB/W MICE

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