Response to 'Statins accelerate the onset of collagen type II-induced arthritis in mice'
© BioMed Central Ltd 2013
Published: 8 March 2013
Statins used to treat hyperlipidemia also exhibit immune-modulatory properties. What is still unclear and a matter of debate, however, is whether these properties are of benefit 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 . According to the authors' conclusion, statins accelerate the onset of CIA in mice. In their study, as previously reported , oral atorvastatin and pravastatin had no effect on the arthritis score after CIA induction. Nonetheless, the oral route might be ineffective due to the significant hepatic first-pass metabolism of statins.
We performed a study that assessed the effects of simvastatin administrated by subcutaneous and intraperitoneal routes in CIA as previously reported . Of the 60 rats included, 50 developed CIA (83.3%) and were treated by daily intraperitoneal simvastatin (n = 5), subcutaneous simvastatin (n = 9), diluted subcutaneous simvastatin (n = 9), subcutaneous 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).
In the intraperitoneal simvastatin group, there was a limitation in the progression of the arthritis score in rats, whereas no effect was noted in the subcutaneous simvastatin group.
Statins may therefore be a therapeutic option in CIA, provided that the substantial effects of hepatic first-pass metabolism are avoided. For CIA treatment, it might thus be interesting to administer transdermal statin patches that enhance diffusion, which have been reported to increase bone formation in rats . Perhaps these patches could also be a therapeutic option in human rheumatoid arthritis.
- Vandebriel RJ, De Jong HJI, Gremmer ER, Klungel OH, 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: R90-10.1186/ar3814.PubMed CentralView ArticlePubMed
- Wahane VD, Kumar VL: Atorvastatin ameliorates inflammatory hyperalgesia in rat model of monoarticular arthritis. Pharmacol Res. 2010, 61: 329-333. 10.1016/j.phrs.2009.11.006.View ArticlePubMed
- Leung BP, Sattar N, Crilly A, Prach M, McCarey DW, Payne H, Madhok R, Campbell C, Gracie JA, Liew FY, McInnes IB: A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol. 2003, 170: 1524-1530.View ArticlePubMed
- Gutierrez GE, Lalka D, Garrett IR, Rossini G, Mundy GR: Transdermal application of lovastatin to rats causes profound increases in bone formation and plasma concentrations. Osteoporos Int. 2006, 17: 1033-1042. 10.1007/s00198-006-0079-0.View ArticlePubMed