Abstracts (complete list) - Wissenschaft Online

Patrick Vollmar, Stefan Nessler, Bianca Wolff, Sudhakar Reddy Kalluri, Hans-Peter
Hartung, Bernhard Hemmer
Preventive and therapeutic effects of the antidepressant
venlafaxine on murine experimental autoimmune
encephalomyelitis
Antidepressants, which are in use for the treatment of major depression, are known to
impact on the immune system. In this study, we examined the immunomodulatory
properties of venlafaxine, a selective serotonin-/norepinephrine reuptake inhibitor, in
murine experimental autoimmune encephalomyelitis (EAE), a Th1-mediated central
nervous system demyelinating disease model of multiple sclerosis. EAE was induced in
SJL mice by adoptive transfer of PLP-specific T-cells. Mice received different doses of
venlafaxine before transfer and after onset of disease. Sustained oral treatment with
6mg and 60mg/kg per day significantly ameliorated the clinical course of disease
compared to vehicle during both preventive and therapeutic intervention. The
ameliorating effect was more pronounced in the high dose group with respect to the
suppression of relapses in the chronic phase of disease. Continuous drug delivery for 14
days was sufficient to delay the onset and peak of disease significantly. However,
ameliorating effects were more pronounced in the sustained treatment experiments.
Disease modifying effects are mediated by venlafaxine’s potential to reduce the
secretion of the Th1 cytokines TNF-alpha and IFN-gamma in encephalitogenic T cell
clones and lines. It further suppressed significantly the mRNA gene expression of
proinflammatory cytokines IFN-gamma, TNF-alpha and the chemokine RANTES in the
spinal cord of EAE mice. These findings demonstrate the strong immunomodulatory
property of the antidepressant venlafaxine and pioneer further studies to clarify whether
venlafaxine may exert similar effects in MS.