Statins have no effect on collagen-induced arthritis in mice
© The Author(s) 2004
Received: 16 January 2004
Published: 25 February 2004
HMG-Co A reductase inhibitors (statins) are widely used lipid-lowering agents. It has recently been shown that, in addition to their well known effect on cholesterol levels, statins display anti-inflammatory activities both in vitro and in vivo. In this context, in vivo prophylactic and therapeutic effects of simvastatin were recently described in mouse collagen-induced arritis, a well-described experimental model for human rheumatoid arthritis (RA).
Objective and Methods
The aim of this study was to investigate further the in vivo effects of three different statins – atorvastatin, rosuvastatin and simvastatin – using the same experimental model. Different doses and routes of administration were used for the various statins in an attempt to elicit antiarthritic activity in preventive and curative treatment protocols.
Atorvastatin and rosuvastatin had no in vivo efficacy, as indicated by clinical, histological (synovial hyperplasia, exsudate and cartilage damage), immunological (anti-type II collagen IgG production and T lymphocyte proliferation) and biochemical (IL-6, serum amyloid A and glucocorticoid production) parameters of inflammation and autoimmunity. The previously described antiarthritic effects of intraperitoneal simvastatin administration were reproduced in our experiments, but could be accounted for by very severe side effects of the treatment leading to increased glucocorticoid levels.
This work shows that statins do not have any effect in a murine model of arthritis; this is an unexpected observation, given the previously described therapeutic effect of statins in immune-mediated inflammatory diseases. It is still unclear whether statins might have a benefit in rheumatic diseases.