{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:47:48Z","timestamp":1790801268667,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,28]],"date-time":"2017-11-28T00:00:00Z","timestamp":1511827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>A crosstalk between the immune system and depression has been postulated, with monocytes\/macrophages and cytokines having a key role in this interaction. In this study, we examined whether vortioxetine, a multimodal anti\u2010depressive drug, was endowed with anti\u2010inflammatory and antioxidative activity, leading to immunomodulatory effects on human monocytes and macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>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\u2010radical and TNF\u03b1 production, TNF\u03b1 and PPAR\u03b3 gene expression and NF\u2010\u03baB translocation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Vortioxetine significantly reduced the PMA\u2010induced 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 in the expression of the surface marker CD86 and an increase in CD206. Moreover, treatment of monocytes with vortioxetine rendered macrophages derived from this population less sensitive to PMA, as it reduced the oxidative burst, NF\u2010kB translocation, TNF\u03b1 release and expression while inducing PPAR\u03b3 gene expression. FACS analysis showed a significant decrease in the CD14<jats:sup>+<\/jats:sup>\/CD16<jats:sup>+<\/jats:sup>\/CD86<jats:sup>+<\/jats:sup> M1 population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These results demonstrate that in human monocytes\/macrophages, vortioxetine has antioxidant activity and anti\u2010inflammatory effects driving the polarization of macrophages towards their alternative phenotype. These findings suggest that vortioxetine, alongside its antidepressive effect, may have immunomodulatory properties.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14074","type":"journal-article","created":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T02:12:35Z","timestamp":1508724755000},"page":"113-124","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Vortioxetine exerts anti\u2010inflammatory and immunomodulatory effects on human monocytes\/macrophages"],"prefix":"10.1111","volume":"175","author":[{"given":"Maria","family":"Talmon","sequence":"first","affiliation":[{"name":"Department of Health Sciences, School of Medicine University of Piemonte Orientale  Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, School of Medicine University of Piemonte Orientale  Novara 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