OBJECTIVE

To study the effect of fluoxetine on Th17- and Th1-immune response, which plays an important role in the pathogenesis of multiple sclerosis (MS).

MATERIAL AND METHODS

Ten patients with relapsing-remitting MS and ten healthy subjects were examined. The functions of Th17- and Th1-immune responses were assessed by the production of cytokines interleukin-17 (IL-17) and interferon-gamma (IFN-γ) by CD4⁺ T cells stimulated with macrophages or microbeads coated with anti-CD3 and anti-CD28-antibodies. To assess the effect of fluoxetine on the macrophages-induced Th17- and Th1-immune response, macrophages were pre-incubated in the presence of fluoxetine and co-cultured with autologous CD4⁺ T-cells. In the case of stimulation of CD4⁺ T-cells with anti-CD3/CD28-microbeads, fluoxetine was added directly to the T-helper cells before adding of microbeads. In addition, we evaluated the effect of fluoxetine on the production of the factors of differentiation of Th17-cells cytokines IL-6 and IL-1β by macrophages. The levels of cytokines in the cell culture supernatants were measured by ELISA.

RESULTS

The production of IL-17 and IFN-γ by CD4⁺ T-cells stimulated with macrophages or anti-CD3/CD28-microbeads was comparable between the groups. Fluoxetine suppressed the production of IL-17 and IFN-γ by anti-CD/CD28-stimulated CD4⁺ T-cells in both groups. Fluoxetine also suppressed the production of IL-6 and IL-1β by macrophages as well as their ability to induce IL-17 and IFN-γ production by CD4⁺ T-cells in both groups.

CONCLUSIONS

Fluoxetine may have an anti-inflammatory effect in MS that could be mediated by suppression of Th17- and Th1-cells or macrophage-induced Th17- and Th1-immune response.