title: Antidepressant compounds can be both pro- and anti-inflammatory in human hippocampal cells.
abstract: BACKGROUND
  The increasingly recognized role of inflammation in the pathogenesis and prognosis of depression has led to a renewed focus on the immunomodulatory properties of compounds with antidepressant action. Studies have, so far, explored such properties in human blood samples and in animal models.
  
  
  METHODS
  Here we used the more relevant model of human hippocampal progenitor cells exposed to an inflammatory milieu, induced by treatment with IL-1β. This increased the levels of a series of cytokines and chemokines produced by the cells, including a dose- and time-dependent increase of IL-6. We investigated the immunomodulatory properties of four monoaminergic antidepressants (venlafaxine, sertraline, moclobemide, and agomelatine) and two omega-3 polyunsaturated fatty acids (n-3 PUFAs; eicosapentanoic acid [EPA] and docosahexanoic acid [DHA]).
  
  
  RESULTS
  We found that venlafaxine and EPA were anti-inflammatory: venlafaxine decreased IL-6, with a trend for decreases of IL-8 and IP-10, while EPA decreased the levels of IL-6, IL-15, IL-1RA, and IP-10. These effects were associated with a corresponding decrease in NF-kB activity. Unexpectedly, sertraline and DHA had pro-inflammatory effects, with sertraline increasing IFN-α and IL-6 and DHA increasing IL-15, IL-1RA, IFN-α, and IL-6, though these changes were also associated with a decrease in NF-kB activity, suggesting distinct modes of action. Agomelatine and moclobemide had no effect on IL-6 secretion.
  
  
  CONCLUSIONS
  These observations indicate that monoaminergic antidepressants and n-3 PUFAs have distinctive effects on immune processes in human neural cells. Further characterization of these actions may enable more effective personalization of treatment based on the inflammatory status of patients.
authors.affiliation: Section of Stress, Psychiatry and Immunology, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK (Dr Horowitz, Ms Wertz, Ms Zhu, Drs Cattaneo, Musaelyan, Nikkheslat, Pariante, and Zunszain); Department of Basic and Clinical Neuroscience, Centre for the Cellular Basis of Behaviour, The James Black Centre (Thuret); and IRCCS Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy (Dr Cattaneo).
authors.forename: Mark Abie
authors.initials: MA
authors.lastname: Horowitz
authors.affiliation: Section of Stress, Psychiatry and Immunology, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK (Dr Horowitz, Ms Wertz, Ms Zhu, Drs Cattaneo, Musaelyan, Nikkheslat, Pariante, and Zunszain); Department of Basic and Clinical Neuroscience, Centre for the Cellular Basis of Behaviour, The James Black Centre (Thuret); and IRCCS Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy (Dr Cattaneo).
authors.forename: Jasmin
authors.initials: J
authors.lastname: Wertz
authors.affiliation: Section of Stress, Psychiatry and Immunology, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK (Dr Horowitz, Ms Wertz, Ms Zhu, Drs Cattaneo, Musaelyan, Nikkheslat, Pariante, and Zunszain); Department of Basic and Clinical Neuroscience, Centre for the Cellular Basis of Behaviour, The James Black Centre (Thuret); and IRCCS Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy (Dr Cattaneo).
authors.forename: Danhui
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Section of Stress, Psychiatry and Immunology, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK (Dr Horowitz, Ms Wertz, Ms Zhu, Drs Cattaneo, Musaelyan, Nikkheslat, Pariante, and Zunszain); Department of Basic and Clinical Neuroscience, Centre for the Cellular Basis of Behaviour, The James Black Centre (Thuret); and IRCCS Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy (Dr Cattaneo).
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cattaneo
authors.affiliation: Section of Stress, Psychiatry and Immunology, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK (Dr Horowitz, Ms Wertz, Ms Zhu, Drs Cattaneo, Musaelyan, Nikkheslat, Pariante, and Zunszain); Department of Basic and Clinical Neuroscience, Centre for the Cellular Basis of Behaviour, The James Black Centre (Thuret); and IRCCS Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy (Dr Cattaneo).
authors.forename: Ksenia
authors.initials: K
authors.lastname: Musaelyan
authors.affiliation: Section of Stress, Psychiatry and Immunology, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK (Dr Horowitz, Ms Wertz, Ms Zhu, Drs Cattaneo, Musaelyan, Nikkheslat, Pariante, and Zunszain); Department of Basic and Clinical Neuroscience, Centre for the Cellular Basis of Behaviour, The James Black Centre (Thuret); and IRCCS Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy (Dr Cattaneo).
authors.forename: Naghmeh
authors.initials: N
authors.lastname: Nikkheslat
authors.affiliation: Section of Stress, Psychiatry and Immunology, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK (Dr Horowitz, Ms Wertz, Ms Zhu, Drs Cattaneo, Musaelyan, Nikkheslat, Pariante, and Zunszain); Department of Basic and Clinical Neuroscience, Centre for the Cellular Basis of Behaviour, The James Black Centre (Thuret); and IRCCS Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy (Dr Cattaneo).
authors.forename: Sandrine
authors.initials: S
authors.lastname: Thuret
authors.affiliation: Section of Stress, Psychiatry and Immunology, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK (Dr Horowitz, Ms Wertz, Ms Zhu, Drs Cattaneo, Musaelyan, Nikkheslat, Pariante, and Zunszain); Department of Basic and Clinical Neuroscience, Centre for the Cellular Basis of Behaviour, The James Black Centre (Thuret); and IRCCS Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy (Dr Cattaneo).
authors.forename: Carmine Maria
authors.initials: CM
authors.lastname: Pariante
authors.affiliation: Section of Stress, Psychiatry and Immunology, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK (Dr Horowitz, Ms Wertz, Ms Zhu, Drs Cattaneo, Musaelyan, Nikkheslat, Pariante, and Zunszain); Department of Basic and Clinical Neuroscience, Centre for the Cellular Basis of Behaviour, The James Black Centre (Thuret); and IRCCS Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy (Dr Cattaneo). patricia.zunszain@kcl.ac.uk.
authors.forename: Patricia Ana
authors.initials: PA
authors.lastname: Zunszain
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D016207:Cytokines; D015525:Fatty Acids, Omega-3; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger
keywords: cytokines; depression; inflammation; neural stem cells; omega-3 fatty acids