Cyclophosphamide Treatment of Kidney Disease in (Nzb X Nzw) F1 Mice

Russell, PamelaJ.; Hicks, John; Burnet, F. M.

doi:10.1016/s0140-6736(66)91198-6

Cited by 66 publications

(30 citation statements)

References 15 publications

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“…Previous studies in B/W mice demonstrated that CTX is very effective in treating murine lupus, especially lupus nephritis (1)(2)(3)(4). Comparison studies in B/W mice (23) and humans (24) established it as the most effective of various immunosuppressive drugs commonly used in human SLE.…”

Section: Discussionmentioning

confidence: 99%

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Cutting Edge: Reversal of Murine Lupus Nephritis with CTLA4Ig and Cyclophosphamide

Daikh

Wofsy

2001

The Journal of Immunology

189

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Cyclophosphamide (CTX) prevents progression of nephritis and prolongs survival in (NZB × NZW)F1 (B/W) mice and is used to treat humans with lupus nephritis. To compare the efficacy of CTLA4Ig with CTX and determine whether there is an incremental benefit to combining CTLA4Ig with CTX, we treated B/W mice with CTX, CTLA4Ig, or both agents. In mice with mild renal disease, treatment delayed the onset of proteinuria and prolonged survival in all groups. In mice with advanced renal disease, treatment with both agents reduced proteinuria in 71% of mice, whereas mice treated with either agent alone had no such improvement. Survival was also markedly improved among mice treated with both agents. Thus, combination treatment with CTX and CTLA4Ig is more effective than either agent alone in reducing renal disease and prolonging survival of B/W mice with advanced nephritis. This striking reversal of proteinuria is unprecedented in animal models of SLE.

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Section: Discussionmentioning

confidence: 99%

“…Early studies in this murine model showed that administration of the alkylating agent cyclophosphamide (CTX) significantly retarded the progression of kidney disease (1)(2)(3)(4). After demonstration of similar results in humans, CTX has become the primary drug used for diffuse proliferative glomerulonephritis among patients with renal lupus (5).…”

mentioning

confidence: 99%

Cutting Edge: Reversal of Murine Lupus Nephritis with CTLA4Ig and Cyclophosphamide

Daikh

Wofsy

2001

The Journal of Immunology

189

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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).…”

mentioning

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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“…Many immunosuppressive regimens have been found useful in murine lupus (2-1 3). In particular, cyclophosphamide (Cy) has been demonstrated to be very effective in treating the glomerulonephritis of NZB/NZW F, mice (2,3,(6)(7)(8)(9). Indeed this drug has been used to treat patients with SLE (14).…”

Section: Therapeutic Studies In Nzb/nzw F Mice V Comparison Of Cyclmentioning

confidence: 99%

Therapeutic Studies in NZB/NZW F₁ Mice

Gerber¹,

Powell²,

Steinberg³

1977

Arthritis & Rheumatism

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Cyclophosphamide (Cy ) has been demonstrated to be effective in treating autoimmune disease in NZB/NZW F, mice. This study was designed to compare the efficacy of chlorambucil (Chlor) with that of a known effective drug (Cy) in the treatment of murine lupus. NZB/W female mice were treated with Cy, Chlor, or nothing on a once-a-month dosage schedule. The age of onset of proteinuria, the severity of glomerular lesions, and the median survival were compared among the three treatment groups. Cy was found to be superior to Chlor and controls in all measures. NZB/NZW F, mice develop an autoimmune disease characterized by immune complex glomerulonephritis, lymphoid infiltrates of many organs, and shortened life expectancy ( I ) . These mice share certain features with patients with systemic lupus erythematosus (SLE), most notably antinuclear antibodies and immune complex glomerulonephritis. As a result, NZ mice have been an important model for studying the pathogenesis of SLE.

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Cyclophosphamide Treatment of Kidney Disease in (Nzb X Nzw) F1 Mice

Cited by 66 publications

References 15 publications

Cutting Edge: Reversal of Murine Lupus Nephritis with CTLA4Ig and Cyclophosphamide

Cutting Edge: Reversal of Murine Lupus Nephritis with CTLA4Ig and Cyclophosphamide

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

Therapeutic Studies in NZB/NZW F₁ Mice

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Cyclophosphamide Treatment of Kidney Disease in (Nzb X Nzw) F1 Mice

Cited by 66 publications

References 15 publications

Cutting Edge: Reversal of Murine Lupus Nephritis with CTLA4Ig and Cyclophosphamide

Cutting Edge: Reversal of Murine Lupus Nephritis with CTLA4Ig and Cyclophosphamide

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

Therapeutic Studies in NZB/NZW F1 Mice

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Therapeutic Studies in NZB/NZW F₁ Mice