Prevention and treatment of experimental crescentic glomerulonephritis by blocking tumour necrosis factor‐α

Karkar, Ayman; Smith, Jennifer; Pusey, Charles D.

doi:10.1093/ndt/16.3.518

Cited by 88 publications

(71 citation statements)

References 23 publications

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“…Many investigators have performed various treatments to reduce these factors in experimental crescentic GN. 5,[37][38][39] The administration of micro-encapsulated clodronate (dichloromethylene bisphosphonate) for macrophage depletion, 37 monoclonal antibodies against CD4, 37 IFNg, 5 and MCP-1, 38 and the soluble TNF receptor p55, 39 prevent glomerular macrophage infiltration, crescent formation, and proteinuria. In the present study, continuous high-level vIL-10 delivery by hydrodynamicsbased transfection suppressed these factors simultaneously.…”

Section: Discussionmentioning

confidence: 99%

Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar–Kyoto rats

et al. 2003

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Gene therapy is expected to revolutionize the treatment of kidney diseases. Viral interleukin (vIL)-10 has a variety of immunomodulatory properties. We examined the applicability of vIL-10 gene transfer to the treatment of rats with crescentic glomerulonephritis, a T helper 1 (Th 1) predominant disease. To produce the disease, Wistar-Kyoto rats were injected with a rabbit polyclonal anti-rat glomerular basement membrane antibody. After 3 h, a large volume of plasmid DNA expressing vIL-10 (pCAGGS-vIL-10) solution was rapidly injected into the tail vein. pCAGGS solution was similarly injected into control rats (pCAGGS rats). We confirmed the presence of vector-derived vIL-10 mainly in the liver and observed high serum vIL-10 levels in pCAGGSvIL-10-injected rats. Compared with the pCAGGS rats, the pCAGGS-vIL-10 rats showed significant therapeutic effects: reduced frequency of crescent formation, decrease in the number of total cells, macrophages, and CD4 + T cells in the glomeruli, decrease in urine protein, and attenuation of kidney dysfunction. Using quantitative real-time polymerase chain reaction, we also observed that this model was Th1-predominant in the glomeruli and that the ratio of the transcripts of CD4, interferon-g, tumor necrosis factor-a, and monocyte chemotactic protein-1 to the transcripts of glucose-6-phosphate dehydrogenase in the glomeruli were all significantly lower in the pCAGGS-vIL-10 rats than in the pCAGGS rats. These results demonstrate that pCAGGS-vIL-10 gene transfer by hydrodynamics-based transfection suppresses crescentic glomerulonephritis.

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Section: Discussionmentioning

confidence: 99%

Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar–Kyoto rats

et al. 2003

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“…In a similar manner to that shown in rheumatoid patients, treatment of patients suffering from ANCA-associated systemic vasculitis with anti-TNF monoclonal antibody may result in deactivation of the endothelium, reducing interactions between endothelial adhesion molecules and the counter ligands expressed on leukocytes, consequently reducing retention of circulating leukocytes in inflamed tissues. Recent evidence has shown benefit of TNF blockade in an animal model of acute crescentic glomerulonephritis, a model of human renal vasculitis (52).…”

Section: Rescue Therapy For Refractory and Relapsing Diseasementioning

confidence: 99%

ANCA-Positive Vasculitis

Kamesh

Harper

Savage

2002

Journal of the American Society of Nephrology

109

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“…TNF-deficient mice subjected to nephrotoxic nephritis demonstrate a partial reduction in proteinuria, glomerular crescent formation, infiltration of leukocytes, and expression of vascular adhesion molecules (6,7). Anti-TNF antibodies attenuate acute glomerular injury in anti-GBM antibody-induced GN in rats (8), and administration of soluble TNF receptors (TNFRs), which neutralize biological TNF activity, reduces glomerular lesions and prevents crescent formation in rats developing crescentic GN (9,10). TNF is produced predominantly by macrophages and T cells, but neutrophils, mast cells, and endothelium also express it (11).…”

Section: Introductionmentioning

confidence: 99%

Renal cell–expressed TNF receptor 2, not receptor 1, is essential for the development of glomerulonephritis

Vielhauer

Stavrakis²,

Mayadas³

2005

J. Clin. Invest.

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TNF is essential for the development of glomerulonephritis, an immune-mediated disorder that is a major cause of renal failure worldwide. However, TNF has proinflammatory and immunosuppressive properties that may segregate at the level of the 2 TNF receptors (TNFRs), TNFR1 and TNFR2. TNFR1-deficient mice subjected to immune complex-mediated glomerulonephritis developed less proteinuria and glomerular injury, and fewer renal leukocyte infiltrates at early time points after disease induction, and this was associated with a reduced systemic immune response to nephrotoxic rabbit IgG. However, proteinuria and renal pathology were similar to those in wild-type controls at later time points, when lack of TNFR1 resulted in excessive renal T cell accumulation and an associated reduction in apoptosis of these cells. In sharp contrast, TNFR2-deficient mice were completely protected from glomerulonephritis at all time points, despite an intact systemic immune response. TNFR2 was induced on glomerular endothelial cells of nephritic kidneys, and TNFR2 expression on intrinsic cells, but not leukocytes, was essential for glomerulonephritis and glomerular complement deposition. Thus, TNFR1 promotes systemic immune responses and renal T cell death, while intrinsic cell TNFR2 plays a critical role in complement-dependent tissue injury. Therefore, therapeutic blockade specifically of TNFR2 may be a promising strategy in the treatment of immune-mediated glomerulonephritis.

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Prevention and treatment of experimental crescentic glomerulonephritis by blocking tumour necrosis factor‐α

Cited by 88 publications

References 23 publications

Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar–Kyoto rats

Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar–Kyoto rats

ANCA-Positive Vasculitis

Renal cell–expressed TNF receptor 2, not receptor 1, is essential for the development of glomerulonephritis

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