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International Journal of Endocrinology
Volume 2012 (2012), Article ID 417017, 8 pages
http://dx.doi.org/10.1155/2012/417017
Research Article

Preventive Treatment with Methylprednisolone Paradoxically Exacerbates Experimental Autoimmune Encephalomyelitis

1Institute for Multiple Sclerosis Research, University of Göttingen and Gemeinnützige Hertie-Stiftung, Waldweg 33, 37073 Göttingen, Germany
2Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD 20892, USA
3Institute of Cellular and Molecular Immunology, University of Göttingen Medical School, Humboldtallee 34, 37073 Göttingen, Germany
4Department of Laboratory Animal Science, Medical School, University of Greifswald, Walther-Rathenau-Straße 49a, 17489 Greifswald, Germany

Received 14 August 2012; Revised 22 October 2012; Accepted 2 November 2012

Academic Editor: Andrew Chan

Copyright © 2012 Simone Wüst et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Glucocorticoids (GCs) represent the standard treatment for acute disease bouts in multiple sclerosis (MS) patients, for which methylprednisolone (MP) pulse therapy is the most frequently used protocol. Here, we compared the efficacy of therapeutic and preventive MP application in -induced experimental autoimmune encephalomyelitis (EAE) in C57Bl/6 mice. When administered briefly after the onset of the disease, MP efficiently ameliorated EAE in a dose-dependent manner. Surprisingly, MP administration around the time of immunization was contraindicated as it even increased leukocyte infiltration into the CNS and worsened the disease symptoms. Our analyses suggest that in the latter case an incomplete depletion of peripheral T cells by MP triggers homeostatic proliferation, which presumably results in an enhanced priming of autoreactive T cells and causes an aggravated disease course. Thus, the timing and selection of a particular GC derivative require careful consideration in MS therapy.