Short report

Simvastatin inhibits interferon-γ-induced MHC class II up-regulation in cultured astrocytes

Esther Zeinstra¹ , Nadine Wilczak¹ , Daniel Chesik¹ , Lisa Glazenburg^1,2 , Frans GM Kroese² and Jacques De Keyser¹

¹  Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

²  Cell Biology (Immunology Section), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

author email corresponding author email

Journal of Neuroinflammation 2006, 3:16doi:10.1186/1742-2094-3-16

Published:	21 July 2006

Abstract

Based on their potent anti-inflammatory properties and a preliminary clinical trial, statins (HMG-CoA reductase inhibitors) are being studied as possible candidates for multiple sclerosis (MS) therapy. The pathogenesis of MS is unclear. One theory suggests that the development of autoimmune lesions in the central nervous system may be due to a failure of endogenous inhibitory control of MHC class II expression on astrocytes, allowing these cells to adapt an interferon (IFN)-γ-induced antigen presenting phenotype. By using immunocytochemistry in cultured astrocytes derived from newborn Wistar rats we found that simvastatin at nanomolar concentrations inhibited, in a dose-response fashion, up to 70% of IFN-γ-induced MHC class II expression. This effect was reversed by the HMG-CoA reductase product mevalonate. Suppression of the antigen presenting function of astrocytes might contribute to the beneficial effects of statins in MS.