Atorvastatin enhances humoral immune responses but does not alter renal injury in experimental crescentic glomerulonephritis

• Published in: Nephrology (Carlton, Vic.) Vic.), 2009-10, Vol.14 (7), p.650-657
• Main Authors: PHOON, RICHARD K S, KITCHING, A RICHARD, JONES, LYNELLE K, HOLDSWORTH, STEPHEN R
• Format: Article
• Language: English
• Subjects: Animals; Atorvastatin Calcium; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Dose-Response Relationship, Drug; glomerulonephritis; Glomerulonephritis - drug therapy; Glomerulonephritis - immunology; Glomerulonephritis - pathology; Heptanoic Acids - pharmacology; HMG-CoA reductase; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Immunity, Humoral - drug effects; immunomodulatory; inflammation; Kidney - drug effects; Kidney - pathology; Male; Mice; Mice, Inbred C57BL; Pyrroles - pharmacology; statin
• ISSN: 1320-5358; 1440-1797
• DOI: 10.1111/j.1440-1797.2009.01141.x

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.