statins accelerate the onset of collagen type ii-induced arthritis in mice他汀类药物加速胶原蛋白类型ii-induced关节炎发作的老鼠.pdfVIP

Vandebriel et al. Arthritis Research Therapy 2012, 14:R90 /content/14/2/R90 RESEARCH ARTICLE Open Access Statins accelerate the onset of collagen type II-induced arthritis in mice 1* 1,2,3 1 3 4 Rob J Vandebriel , Hilda JI De Jong , Eric R Gremmer , Olaf H Klungel , Jan-Willem Cohen Tervaert , Wout Slob5, Jan Willem Van Der Laan6 and Henk Van Loveren1,2 Abstract Introduction: Statins (hydroxymethylglutaryl coenzyme A 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 (day 21 until day 42) CIA induction. Atorvastatin (0.2 mg/day) or pravastatin (0.8 mg/day) was administered. Arthritis was recorded three times a week. Serum anti-CII autoantibodies and cytokines in supernatants from Concanavalin-A-stimulated lymph node cells and CII-stimulated spleen cells were measured. Results: Statin administration accelerated arthritis onset and resulted in 100% arthritic animals, whereas