The antidepressant venlafaxine ameliorates murine experimental autoimmune encephalomyelitis

Antidepressants, which are in use for the treatment of major depression, are known to impact on the immune system. Here, 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 were treated with 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. This 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. Venlafaxine affected the secretion of the Th1 cytokines TNF-alpha and IFN-gamma in encephalitogenic T cell clones and lines but had only minor effects on Th2 cytokines. These findings demonstrate the strong immunomodulatory property of the antidepressant venlafaxine. Further studies are warranted to clarify whether venlafaxine may exert similar effects in MS.