Abstracts (complete list) - Wissenschaft Online

Simone Wüst, Denise Tischner, Anna Kleimann, Ralf Gold, Jan P. Tuckermann, Holger
M. Reichardt, Fred Lühder
Analysis of Glucocorticoid action in
Experimental Autoimmune Encephalomyelitis (EAE)
Currently application of high-dose glucocorticoids (GCs) is the standard therapy of acute
relapses in multiple sclerosis. Despite their widespread use, the mechanisms of GC
action in the treatment of neuroinflammatory disorders are not yet fully understood.
This refers to the cell-types that are targets of GCs, the question whether genomic or
rather non-genomic mechanisms are involved and the processes that are modulated. In
order to address these questions, we made use of the well-established MOG35-55
induced EAE model in the C57Bl/6 mouse.
Therapeutic and preventive administration of dexamethasone ameliorates the disease
course in a dose-dependent manner. To elucidate the role of the GR in mediating this
effect we used heterozygous GR knock-out mice and hematopoietic stem cell chimeras.
These experiments revealed that the cytosolic GR is a prerequisite for most GC actions
since the therapeutic efficacy of high doses of dexamethasone was very low and
transient in these models as demonstrated by the clinical scores and histological
analysis of CNS inflammation. Induction of EAE in different conditional GR knock-out
mice showed that, at the cellular level, expression of the GR in T cells is essential for
the beneficial effects of GCs in neuroinflammatory diseases. At present experiments are
under way that should help to identify the processes and genes that are specifically
targeted by GCs in T cells. With the new knowledge in hands we anticipate that
therapeutic approaches for multiple sclerosis may be improved.