Response to 'Statins accelerate the onset of collagen type II-induced arthritis in mice'

used to treat hyperlipidemia also exhibit immuno-modulatory properties. What is still unclear and a matter of debate, however, is whether these properties are of benefi t or are deleterious in collagen type II-induced arthritis (CIA). We read with great interest Vandebriel and colleagues' article about the role of statins in the induction of CIA [1]. According to the authors' conclusion, statins accelerate the onset of CIA in mice. In their study, as previously reported [2], oral atorvastatin and pravastatin had no eff ect on the arthritis score after CIA induction. Nonetheless , the oral route might be ineff ective due to the signifi cant hepatic fi rst-pass metabolism of statins. We performed a study that assessed the eff ects of simvastatin administrated by subcutaneous and intra-peri to neal routes in CIA as previously reported [3]. Of the 60 rats included, 50 developed CIA (83.3%) and were treated by daily intra peritoneal simvastatin (n = 5), subcutaneous simvastatin (n = 9), diluted subcutaneous simvastatin (n = 9), sub cutaneous saline (n = 9), and intraperitoneal saline (n = 9) for a total of 15 days. Nine rats received no treatment. A total score was calculated by grading each joint of the four limbs using a scale of 0 to 3 (0 = normal, 1 = erythema, 2 = erythema + swelling, and 3 = loss of function). At baseline, no diff erence was noted in the arthritis score or weight between groups. We observed a significant weight decrease in each treatment group but no diff erence in weight loss between groups. After adjusting for weight, there was a signifi cant diff erence in arthritis scores between intraperitoneal simvastatin and the other groups, with signifi cantly lower arthritis scores obtained in the intraperitoneal simvastatin group (Figure 1). Th e diff erence of the arthritis score between subcutaneous simvastatin and intraperitoneal simvastatin was significant (P = 0.002) (intraperitoneal: 3.67 ± 1.32 at baseline and 4.89 ± 1.69 after 15 days vs. subcutaneous: 4.20 ± 0.84 at baseline and 7.40 ± 1.34 after 15 days). Diff erences in arthritis scores between the other groups, except for the simvastatin group, were not signifi cant (Figure 1). Th ese results obtained using linear mixed-models analysis were similar to those obtained when using PROAST, a general program for dose–response modeling, as in Vandebriel and colleagues' article. In the intraperitoneal simvastatin group, there was a limitation in the …