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Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin

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Item Type:Article
Title:Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin
Creators Name:Aktas, O. and Waiczies, S. and Smorodchenko, A. and Dorr, J. and Seeger, B. and Prozorovski, T. and Sallach, S. and Endres, M. and Brocke, S. and Nitsch, R. and Zipp, F.
Abstract:Statins, known as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, exhibit numerous functions related to inflammation, such as MHC class II down-regulation, interference with T cell adhesion, and induction of apoptosis. Here we demonstrate that both subcutaneous and oral administration of atorvastatin inhibit the development of actively induced chronic experimental autoimmune encephalomyelitis in SJL/J mice and significantly reduce the inflammatory infiltration into the central nervous system (CNS). When treatment was started after disease onset, atorvastatin reduced the incidence of relapses and protected from the development of further disability. Both the reduced autoreactive T cell response measured by proliferation toward the encephalitogenic peptide PLP139-151 and the cytokine profile indicate a potent blockade of T helper cell type 1 immune response. In in vitro assays atorvastatin not only inhibited antigen-specific responses, but also decreased T cell proliferation mediated by direct TCR engagement independently of MHC class II and LFA-1. Inhibition of proliferation was not due to apoptosis induction, but linked to a negative regulation on cell cycle progression. However, early T cell activation was unaffected, as reflected by unaltered calcium fluxes. Thus, our results provide evidence for a beneficial role of statins in the treatment of autoimmune attack on the CNS.
Keywords:EAE, Multiple Sclerosis, HMG-CoA Reductase, T Cell, Autoimmunity, Animals, Inbred Strains Mice, Mice
Source:Journal of Experimental Medicine
Publisher:Rockefeller University Press
Page Range:725-733
Date:17 March 2003
Official Publication:https://doi.org/10.1084/jem.20021425
PubMed:View item in PubMed

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