Atorvastatin enhances humoral immune responses but does not alter renal injury in experimental crescentic glomerulonephritis.
Nephrology (Carlton)
; 14(7): 650-7, 2009 Oct.
Article
en En
| MEDLINE
| ID: mdl-19796023
AIM: Statins are widely used for their cholesterol-lowering effects and for prevention of cardiovascular disease. Evidence indicates that these drugs also have immunomodulatory and other non-lipid lowering effects, with studies suggesting benefit in some animal models of immune (particularly T helper (Th)1)-mediated inflammatory disease and their corresponding human disease counterparts. We sought to evaluate the immunomodulatory effects and therapeutic potential of atorvastatin in experimental crescentic glomerulonephritis, a Th1-predominant animal model of glomerulonephritis. METHODS: Autologous phase, anti-glomerular basement membrane glomerulonephritis was induced in C57BL/6 mice by intravenous injection of sheep anti-mouse glomerular basement membrane globulin. Mice were administered atorvastatin (10 or 100 mg/kg) or control (phosphate-buffered saline) daily by oral gavage. Immune responses and renal injury were assessed after 21 days. RESULTS: Compared with control-treated mice, treatment with atorvastatin did not alter renal injury (serum creatinine, proteinuria, glomerular crescent formation) or glomerular leukocytic infiltration (CD4(+) T cells or macrophages). Atorvastatin resulted in a dose-related increase in circulating serum antibody to the disease-inducing antigen but no differences in antigen-stimulated splenocyte production of Th1/Th2 cytokines. At the higher dose, atorvastatin also led to a significant reduction in apoptosis of splenic CD4(+) T lymphocytes. CONCLUSION: This study demonstrates that statins modulate humoral responses and alter splenic CD4(+) T cell apoptosis. However, atorvastatin does not lead to significant changes in T helper cell polarization or renal injury in experimental crescentic glomerulonephritis.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirroles
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Inhibidores de Hidroximetilglutaril-CoA Reductasas
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Inmunidad Humoral
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Glomerulonefritis
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Ácidos Heptanoicos
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Riñón
Límite:
Animals
Idioma:
En
Revista:
Nephrology (Carlton)
Asunto de la revista:
NEFROLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Australia