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

The increasingly recognised 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. 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). We found that venlafaxine and EPA were anti-inflammatory: venlafaxine decreased IL-6, with a trend for decrease 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, increasing IFN-α and IL-6, and IL-15, IL-1RA, IFN-α and IL-6, respectively, 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. These observations indicate that monoaminergic antidepressants and n-3 PUFAs have distinctive effects on immune processes in human neural cells. Further characterisation of these actions may enable more effective personalisation of treatment based on the inflammatory status of patients.