Vortioxetine exerts anti‐inflammatory and immunomodulatory effects on human monocytes/macrophages

Background and Purpose A crosstalk between the immune system and depression has been postulated, with a key role played by monocytes/macrophages and cytokines. In this paper we examined whether vortioxetine, a multimodal anti-depressive drug, was endowed of antiinflammatory and anti-oxidative activity, leading to immunomodulatory effects on human monocytes and macrophages. Experimental Approaches Human monocytes were isolated from buffy coats and used as such or differentiated into M1 and M2 macrophages. Cells were treated with vortioxetine before or after differentiation, and their responsiveness was evaluated. This included oxy-radical and TNFα production, TNFα and PPARγ gene expression, and NF-κB translocation. Key results Vortioxetine significantly reduced the PMA-induced oxidative burst in monocytes and in macrophages (M1 and M2), causing a concomitant shift of macrophages from the M1 to the M2 phenotype, demonstrated by a significant decrease of the expression of the surface marker CD86 and an increase of CD206. Moreover, treatment of monocytes with vortioxetine rendered macrophages derived from this population less sensitive to PMA, as it reduced the oxidative burst, NF-kB translocation, TNFα release and expression, while inducing PPARγ gene expression. FACS analysis showed a significant decrease of the CD14+/CD16+/CD86+ M1 population. Conclusion and Implications These results demonstrate that in human monocytes/macrophages vortioxetine is endowed of an anti-oxidant activity and antiinflammatory effects driving polarization of macrophages toward the alternative phenotype. Our findings therefore suggest that vortioxetine, alongside its antidepressive effect, may have immunomodulatory properties.