Statins accelerate the onset of collagen type II-induced arthritis in mice. - GreenMedInfo Summary
Statins accelerate the onset of collagen type II-induced arthritis in mice.
Arthritis Res Ther. 2012 Apr 26 ;14(2):R90. Epub 2012 Apr 26. PMID: 22537858
ABSTRACT: INTRODUCTION: Statins (hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors) are effective in reducing the risk of cardiovascular morbidity and mortality in patients with hyperlipidemia, hypertension, or type II diabetes. Next to their cholesterol lowering activity, statins have immunomodulatory properties. Based on these properties, we hypothesized that statin use may eventually lead to dysregulation of immune responses, possibly resulting in autoimmunity. We have recently shown in an observational study that statin use was associated with an increased risk of developing rheumatoid arthritis. Our objective was to investigate whether a causal relationship could be established for this finding. METHODS: The mouse collagen type II (CII)-induced arthritis (CIA) model was used, with immunization, challenge, and euthanasia at days 0, 21, and 42, respectively. Statins were given orally before (day -28 until day 21) or after CIA induction (day 21 until day 42). Atorvastatin (0.2 mg/day) or pravastatin (0.8 mg/day) was given. Arthritis was recorded 3 times a week. Serum anti-CII autoantibodies, and cytokines in supernatants from Concanavalin A-stimulated lymph node (LN) cells and CII-stimulated spleen cells were measured. RESULTS: Statin administration accelerated arthritis onset and resulted in 100% arthritic animals, whereas in the non-statin controls only 7 out of 12 animals developed arthritis. Atorvastatin administration after CIA induction resulted in earlier onset than atorvastatin administration before induction, or pravastatin administration before or after induction. The arthritic score of animals given pravastatin before CIA induction was similar to that of the non-statin controls, whereas the other groups that received statins showed higher arthritic scores. Atorvastatin administration, especially before CIA induction, increased anti-CII autoantibody production. Interleukin-2 (IL-2) and interleukin-17 (IL-17) production by LN and spleen cells was higher in CIA animals than in phosphate buffered saline (PBS) controls, but was not affected by statin administration. While interferon-gamma (IFN-*) production was not affected by CIA induction, atorvastatin administration before CIA induction increased the production of this cytokine. CONCLUSIONS: These data support previous results from our observational studies, indicating a role for statins in the induction of autoimmunity.