15-Deoxyspergualin and cyclophosphamide, but not mycophenolate mofetil, prolong survival and attenuate renal disease in a murine model of ANCA-associated crescentic nephritis

Birck, Rainer; Newman, Mark; Braun, Claude; Neumann, Irmgard; Nemoto, Kyuichi; Yard, Benito A.; Waldherr, Rüdiger; Woude, Fokko J. van der

doi:10.1093/ndt/gfi070

Cited by 19 publications

(13 citation statements)

References 46 publications

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“…Five mice were treated with rapamycin at 5 mg/kg/day and 5 mice were treated with MMF at 100 mg/kg/day intraperitoneally. 11,12 Nine mice received no treatment, representing a cohort from this randomization plus historical controls from the earlier experiments described in this work. Mice were treated for 3 months and lymphadenopathy, splenomegaly, and peripheral blood DNTs were followed serially as described in "Assessment of response to rapamycin treatment: peripheral blood for DNTs.…”

Section: Comparison Of Rapamycin To Mycophenolate Mofetilmentioning

confidence: 99%

Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS)

Teachey

Obzut

Axsom

et al. 2006

Blood

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Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by defective Fas-mediated apoptosis, leading to lymphadenopathy, hepatosplenomegaly, and an increased number of doublenegative T cells (DNTs). Treatment options for patients with ALPS are limited. Rapamycin has been shown to induce apoptosis in normal and malignant lymphocytes. Since ALPS is caused by defective lymphocyte apoptosis, we hypothesized that rapamycin would be effective in treating ALPS. We tested this hypothesis using rapamycin in murine models of ALPS. We followed treatment response with serial assessment of DNTs by flow cytometry in blood and lymphoid tissue, by serial monitoring of lymph node and spleen size with ultrasonography, and by enzyme-linked immunosorbent assay (ELISA) for anti-double-stranded DNA (dsDNA) antibodies. Three-dimensional ultrasound measurements in the mice correlated to actual tissue measurements at death (r ‫؍‬ .9648). We found a dramatic and statistically significant decrease in DNTs, lymphadenopathy, splenomegaly, and autoantibodies after only 4 weeks when comparing rapamycin-treated mice with controls. Rapamycin induced apoptosis through the intrinsic mitochondrial pathway. We compared rapamycin to mycophenolate mofetil, a second-line agent used to treat ALPS, and found rapamycin's control of lymphoproliferation was superior. We conclude that rapamycin is an effective treatment for murine ALPS and should be explored as treatment for affected humans. (Blood. 2006;108: 1965-1971

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Section: Comparison Of Rapamycin To Mycophenolate Mofetilmentioning

confidence: 99%

Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS)

Teachey

Obzut

Axsom

et al. 2006

Blood

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“…Additionally, DSG prolongs survival and attenuates renal disease in a murine model of antineutrophil cytoplasmic antibodies-associated crescentic nephritis. Therefore, DSG may have the potential to treat successfully these most severe forms of human glomerulonephritis [21]. Also, the ability of DSG to suppress systemic lupus erythematosus (SLE)-like diseases has been demonstrated in animals and humans [22,23].…”

Section: Introductionmentioning

confidence: 99%

15-deoxyspergualin prevents mucosal injury by inhibiting production of TNF-α and down-regulating expression of MD-1 in a murine model of TNBS-induced colitis

Lee¹,

Kim²,

Kim³

et al. 2007

International Immunopharmacology

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“…6). Birck et al have found that the prophylactic treatment of SCG/Kj mice at 10 weeks old with DSG at a daily intraperitoneal dose of 2 mg/kg and CYC at a weekly intraperitoneal dose of 50 mg/kg significantly suppressed crescent formation in glomeruli [27]. Treatment with CYC at a daily orally dose of 12 mg/kg in our study might not be a fully effective dose to inhibit crescent formation although leukopenia was significantly accompanied even in this treatment (Fig.…”

Section: Discussionmentioning

confidence: 52%

Evaluation of the ameliorative effects of immunosuppressants on crescentic glomerulonephritis in SCG/Kj mice

Saiga

Yoshida

Nakamura

et al. 2008

International Immunopharmacology

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15-Deoxyspergualin and cyclophosphamide, but not mycophenolate mofetil, prolong survival and attenuate renal disease in a murine model of ANCA-associated crescentic nephritis

Abstract: DSG and CYC, but not MMF, prolong life, limit renal damage and prevent autoantibody formation in SCG/Kj mice.

Cited by 19 publications

References 46 publications

Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS)

Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS)

15-deoxyspergualin prevents mucosal injury by inhibiting production of TNF-α and down-regulating expression of MD-1 in a murine model of TNBS-induced colitis

Evaluation of the ameliorative effects of immunosuppressants on crescentic glomerulonephritis in SCG/Kj mice

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