Abstracts (complete list) - Wissenschaft Online

Denise Tischner, Nora Müler, Jens van den Brandt, Andreas Weishaupt, Holger
Reichardt
Glucocorticoids exert distinct effects on Experimental
Autoimmune Encephalomyelitis
Multiple sclerosis (MS) and its animal model Experimental Autoimmune
Encephalomyelitis (EAE) are chronic inflammatory diseases of the central nervous
system (CNS) of presumed autoimmune origin. Acute relapses of MS are most
commonly treated with high doses of glucocorticoids (GCs). However, severe adverse
effects and incomplete recovery accompany such therapies. Therefore a better
understanding of the mechanisms of GC action in MS is urgently needed. To distinguish
effects of GCs on pathogenic and conventional T cells we induced an AT-EAE by
adoptive transfer of eGFP+ encephalitogenic T lymphocytes into Lewis rats followed by
treatment with 20 mg/kg dexamethason three days after disease induction. This led to
a rapid amelioration of the disease and a reduced infiltration of the spinal cord. We
found that dexamethasone similarly induced apoptosis in pathogenic as well as
conventional T cells, restored the integrity of the blood-brain barrier and downregulated
ICAM-1 and IP-10 expression in the spinal cord. Accumulation of
encephalitogenic T cells in the spleen supported the notion that impaired T cell
migration to the CNS may contribute to therapeutic efficacy. While GCs did not alter the
expression of integrins and the chemokine receptor CXCR-3, we identified cytoskeletal
rearrangements accompanied by the loss of the migratory phenotype. We believe that
this may partially underlie the reduced lymphocyte infiltration of the CNS. We hope that
a better understanding of GC action in the treatment of MS helps to improve the
available therapies.