Atorvastatin attenuates murine anti-glomerular basement membrane glomerulonephritis.
Statins mediate many of their protective effects by lowering lipids as well as by modulating inflammation. Here, we studied their potential immunomodulatory role in renal inflammation using an autoimmune mouse model of anti-glomerular basement membrane glomerulonephritis. Oral treatment with Atorvastatin dramatically reduced albuminuria and histological changes in the kidneys as compared to vehicle-treated control animals. There was a significant decrease in the Th1 and Th17 response in the regional lymph nodes draining the kidneys. This systemic effect was accompanied by decreased infiltration of the kidneys with inflammatory CD4(+) T and Th17 cells, macrophages, and neutrophils in statin-treated mice. Regulatory T cells were not altered in their number, FoxP3 expression, or suppressive capacity, but their interleukin-10 production was significantly increased by statin treatment. Hence, Atorvastatin systemically and locally decreased the Th1 and Th17 response, thereby protecting the mice against anti-glomerular basement membrane glomerulonephritis. Whether statins can be used to treat human autoimmune renal diseases will require more direct studies.
Eller
Philipp
P
Department of Internal Medicine I, Innsbruck Medical University, Innsbruck, Austria. philipp.eller@i-med.ac.at
Eller
Kathrin
K
Wolf
Anna M
AM
Reinstadler
Sebastian J
SJ
Tagwerker
Andrea
A
Patsch
Josef R
JR
Mayer
Gert
G
Rosenkranz
Alexander R
AR
D000818:Animals; D000069059:Atorvastatin; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D050533:Glomerular Basement Membrane / Q000276:immunology / Q000473:pathology; D005921:Glomerulonephritis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006538:Heptanoic Acids / Q000276:immunology* / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011758:Pyrroles / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D016753:Interleukin-10; D000069059:Atorvastatin