title: Preventive treatment with methylprednisolone paradoxically exacerbates experimental autoimmune encephalomyelitis.
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 MOG(35-55)-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.
authors.affiliation: Institute for Multiple Sclerosis Research, University of Göttingen and Gemeinnützige Hertie-Stiftung, Waldweg 33, 37073 Göttingen, Germany ; Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Wüst
authors.forename: Jens
authors.initials: J
authors.lastname: van den Brandt
authors.forename: Holger M
authors.initials: HM
authors.lastname: Reichardt
authors.forename: Fred
authors.initials: F
authors.lastname: Lühder