Antidepressant Compounds Can Be Both Pro- and Anti-Inflammatory in Human Hippocampal Cells

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-1 beta. 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-kappa B activity. Unexpectedly, sertraline and DHA had pro-inflammatory effects, with sertraline increasing IFN-alpha and IL-6 and DHA increasing IL-15, IL-1RA, IFN-alpha, and IL-6, though these changes were also associated with a decrease in NF-kappa B 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.