The role of 5-HT2B-receptors in fluoxetine-mediated modulation of Th17- and Th1-cells in multiple sclerosis

Fluoxetine is a selective serotonin reuptake inhibitor, which also has an immunomodulatory effect. We investigated the effects of fluoxetine and serotonin (5-HT) on the pro-inflammatory Th17- and Th1-cells in 30 patients with relapsing-remitting MS and 20 healthy subjects. Fluoxetine and 5-HT suppressed IL-17, IFN-γ and GM-CSF production by stimulated СD4+ T-cells in both groups. Blockade of 5-HT2B-receptors decreased the inhibitory effect of fluoxetine on cytokine production in MS patients. Finally, 5-HT2B-receptor activation inhibits IL-17, IFN-γ and GM-CSF production in both groups. These data suggest an anti-inflammatory role for fluoxetine in MS, which could be mediated by the activation of 5-HT2B-receptors. [Display omitted] •Fluoxetine and 5-HT suppress Th17-immune response in multiple sclerosis (MS).•Blockade of 5-HT2B-receptors decreases the inhibitory effect of fluoxetine on IL-17, IFN-γ, and GM-CSF production in MS.•Activation of 5-HT2B-receptors reduces IL-17, IFN-γ, and GM-CSF production in MS.