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

  • Rob J Vandebriel1Email author,

    Affiliated with

    • Hilda JI De Jong1, 2, 3,

      Affiliated with

      • Eric R Gremmer1,

        Affiliated with

        • Olaf H Klungel3,

          Affiliated with

          • Jan-Willem Cohen Tervaert4,

            Affiliated with

            • Wout Slob5,

              Affiliated with

              • Jan W Van Der Laan6 and

                Affiliated with

                • Henk Van Loveren1, 2

                  Affiliated with

                  Arthritis Research & Therapy201315:403

                  DOI: 10.1186/ar4170

                  Published: 8 March 2013

                  We thank Mathieu and colleagues for their interest in our recent publication [1] and for reporting their very interesting experiments showing that intraperitoneal but not subcutaneous simvastatin inhibits arthritis progression in the mouse collagen-induced arthritis (CIA) model [2]. These results are in line with those of Palmer and colleagues, who showed that intraperitoneal but not oral simvastatin administration inhibited pre-existing CIA [3].

                  According to Mathieu and colleagues, in our study we found that 'oral atorvastatin and pravastatin had no effect on the arthritis score after CIA induction' [2]. This statement is not correct, however. In our study, the number of arthritic animals increased from seven out of 12 in the nonstatin-treated controls to 12 out of 12 animals given oral atorvastatin and pravastatin, both after CIA induction (Figure 3A in [1]). Moreover, the summed arthritis score increased from 21 in the nonstatin-treated controls to 37 for oral pravastatin and 49 for oral atorvastatin, both after CIA induction (Figure 3B in [1]).

                  Since our aim was to investigate the possible effects of statin intake upon arthritis development and severity, we chose to administer statins orally-the common route of administration for patients receiving statins. The findings from Mathieu and colleagues [2] underscore that statins have an immunomodulatory activity. Altogether, one may conclude that the outcome of statins on immune responses may depend on the type of statin, the dose, and the route of administration. Whereas we acknowledge that statins may have beneficial immunological effects, statins may also play a role in the induction of autoimmunity, as we have also shown in a general population-based study [4].



                  collagen-induced arthritis.


                  Authors’ Affiliations

                  Laboratory for Health Protection Research, National Institute for Public Health and the Environment
                  Department of Toxicogenomics, Maastricht University
                  Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University
                  Department of Internal Medicine, Division of Clinical and Experimental Immunology, University Hospital Maastricht
                  Centre for Substances and Integrated Risk Assessment, National Institute for Public Health and the Environment
                  Section on Pharmacology, Toxicology and Biotechnology (FTBB), Medicines Evaluation Board


                  1. Vandebriel RJ, De Jong HJ, Gremmer ER, Klungel OH, Cohen Tervaert JW, Slob W, Van Der Laan JW, Van Loveren H: Statins accelerate the onset of collagen type II-induced arthritis in mice. Arthritis Res Ther 2012, 14:R90.PubMedView Article
                  2. Mathieu S, Palat S, Pereira B, Kemeny JL, Marceau G, Dubray C, Soubrier M: Response to 'Statins accelerate the onset of collagen type II-induced arthritis in mice'. Arthritis Res Ther 2013, 15:402.PubMedView Article
                  3. Palmer G, Chobaz V, Talabot-Ayer D, Taylor S, So A, Gabay C, Busso N: Assessment of the efficacy of different statins in murine collagen induced arthritis. Arthritis Rheum 2004, 50:4051–4059.PubMedView Article
                  4. De Jong HJ, Klungel OH, van Dijk L, Vandebriel RJ, Leufkens HG, Van Der Laan J, Tervaert JW, Van Loveren H: Use of statins is associated with an increased risk of rheumatoid arthritis. Ann Rheum Dis 2012, 71:648–654.PubMedView Article


                  © BioMed Central Ltd 2013