Abstract
Abstract: :
Purpose: Recent studies have shown that atorvastatin and homologues, such as 3–Hydroxy–3–methyglutaryl–CoA reductase inhibitors, have anti–inflammatory activity, in additional to their major role of regulating lipoprotein metabolism. They have been successfully used in the treatment of experimental autoimmune encephalomyelitis (EAE). We wished to determine whether such a treatment effect would also be applied to autoimmune uveitis. Methods: Uveitis was induced in Lewis rats either by immunization with an uveitogenic peptide, R16, derived from the interphotoreceptor retinoid–binding protein (IRBP) or by adoptive transfer of R16–specific T cells. Atorvastatin was administered orally in 0.5 ml (10 mg kg–1 dose) once daily. For the treatment of actively induced uveitis, rats received treatment starting on the day of immunization with R16 (day 0), or at the beginning of the clinical signs. For the treatment of adoptively transferred uveitis, daily treatment was given on the day of the transfer. Results:The uveitis–induced rats received 10 mg kg–1of atorvastatin daily, at the beginning of immunization (D0) developed milder disease. However, treatment started before the onset of actively induced uveitis (D8) or at the beginning of adoptively transferred disease did not show significant inhibition of uveitis. Conclusion: Unlike EAE, which has been significantly prevented by the treatment of atorvastatin, higher doses of atorvastatin only partially inhibited the actively induced uveitis in Lewis rat and similar treatment did not significantly ameliorate adoptively transferred uveitis, suggesting that this drug has different treatment effect on different autoimmune diseases.
Keywords: uveitis–clinical/animal model • immunomodulation/immunoregulation • inflammation