Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Zitt, E; Eller, K; Huber, JM; Kirsch, AH; Tagwerker, A; Mayer, G; Rosenkranz, AR.
The selective mineralocorticoid receptor antagonist eplerenone is protective in mild anti-GBM glomeru-lonephritis.
Int J Clin Exp Pathol. 2011; 4(6):606-615
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- Führende Autor*innen der Med Uni Graz
- Rosenkranz Alexander
- Co-Autor*innen der Med Uni Graz
- Eller Kathrin
- Kirsch Alexander
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- Abstract:
- BACKGROUND: Growing evidence suggests that blockade of the aldosterone-receptor may preserve kidney function by anti-inflammatory effects independent of the blood pressure. We hypothesized that the selective aldosterone-receptor antagonist eplerenone has a profound anti-inflammatory effect in the autologous phase of anti-glomerular basement membrane (GBM) glomerulonephritis (GN). METHODS: Mice received â200mg/kg body wt/day eplerenone via supplemented chow diet or standard chow starting at the day of immunization with rabbit IgG. Three days later the anti-GBM antibody was injected and the experiments were stopped at day 7 and 14. RESULTS: Mice receiving eplerenone showed significantly decreased albuminuria and glomerular sclerosis at day 7 and 14 after induction of anti-GBM GN. Eplerenone treatment significantly inhibited the infiltration of CD4+, CD8+ T cells and macrophages into the kidneys. Circulating levels and glomerular deposition of autologous IgG were comparable in both groups. At day 7 the pro-inflammatory cytokines MCP-1 and IL-6 were found to be significantly decreased in regional draining lymph nodes of eplerenone-treated mice, whereas the anti-inflammatory cytokine IL-10 was significantly upregulated. In line, splenocytes from eplerenone-treated nephritic mice produced significantly increased IL-10. CONCLUSION: Aldosterone-receptor blockade by eplerenone effectively attenuated proteinuria, kidney damage and the inflammatory response in anti-GBM GN by significantly decreasing pro-inflammatory cytokines in the regional draining lymph nodes of the kidney. Our results suggest that this selective aldosterone receptor antagonist is a possible additional tool in the treatment of GN.
- Find related publications in this database (using NLM MeSH Indexing)
- Albuminuria -
- Aldosterone Antagonists - therapeutic use
- Animals -
- Anti-Glomerular Basement Membrane Disease - immunology
- CD4-Positive T-Lymphocytes - immunology
- CD8-Positive T-Lymphocytes - immunology
- Cytokines - metabolism
- Immunoglobulin G - immunology
- Kidney Glomerulus - immunology
- Lymph Nodes - drug effects
- Male -
- Mice -
- Rabbits -
- Receptors, Aldosterone - antagonists and inhibitors
- Spironolactone - analogs and derivatives
- Spleen - drug effects
- Find related publications in this database (Keywords)
- Aldosterone antagonism
- glomerulonephritis
- eplerenone
- renal inflammation