Antidepressant compounds can be both pro- and anti-inflammatory in human hippocampal cells

Mark A bie Horowitz, Jasmin Wertz, Danhui Zhu, Annamaria Cattaneo, Ksenia Musaelyan, Naghmeh Nikkheslat, Sandrine Thuret, Carmine M aria Pariante, Patricia A na Zunszain

Research output: Contribution to journalArticle

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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.

Original languageEnglish
JournalInternational Journal of Neuropsychopharmacology
Volume18
Issue number3
DOIs
Publication statusPublished - Feb 1 2015

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Antidepressive Agents
Interleukin-6
Anti-Inflammatory Agents
Sertraline
S 20098
Eicosapentaenoic Acid
Omega-3 Fatty Acids
Moclobemide
Interleukin-15
NF-kappa B
Acids
Unsaturated Fatty Acids
Interleukin-8
Interleukin-1
Chemokines
Stem Cells
Animal Models
Cytokines
Inflammation
Therapeutics

Keywords

  • cytokines
  • depression
  • inflammation
  • neural stem cells
  • omega-3 fatty acids

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Antidepressant compounds can be both pro- and anti-inflammatory in human hippocampal cells. / Horowitz, Mark A bie; Wertz, Jasmin; Zhu, Danhui; Cattaneo, Annamaria; Musaelyan, Ksenia; Nikkheslat, Naghmeh; Thuret, Sandrine; Pariante, Carmine M aria; Zunszain, Patricia A na.

In: International Journal of Neuropsychopharmacology, Vol. 18, No. 3, 01.02.2015.

Research output: Contribution to journalArticle

Horowitz, MAB, Wertz, J, Zhu, D, Cattaneo, A, Musaelyan, K, Nikkheslat, N, Thuret, S, Pariante, CMA & Zunszain, PAN 2015, 'Antidepressant compounds can be both pro- and anti-inflammatory in human hippocampal cells', International Journal of Neuropsychopharmacology, vol. 18, no. 3. https://doi.org/10.1093/ijnp/pyu076
Horowitz, Mark A bie ; Wertz, Jasmin ; Zhu, Danhui ; Cattaneo, Annamaria ; Musaelyan, Ksenia ; Nikkheslat, Naghmeh ; Thuret, Sandrine ; Pariante, Carmine M aria ; Zunszain, Patricia A na. / Antidepressant compounds can be both pro- and anti-inflammatory in human hippocampal cells. In: International Journal of Neuropsychopharmacology. 2015 ; Vol. 18, No. 3.
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AU - Wertz, Jasmin

AU - Zhu, Danhui

AU - Cattaneo, Annamaria

AU - Musaelyan, Ksenia

AU - Nikkheslat, Naghmeh

AU - Thuret, Sandrine

AU - Pariante, Carmine M aria

AU - Zunszain, Patricia A na

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N2 - 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.

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