Impact of antidepressants on cytokine production of depressed patients in vitro

Alexander Munzer, Ulrich Sack, Roland Mergl, Jeremias Schönherr, Charlotte Petersein, Stefanie Bartsch, Kenneth C Kirkby, Katrin Bauer, Hubertus Himmerich, Alexander Munzer, Ulrich Sack, Roland Mergl, Jeremias Schönherr, Charlotte Petersein, Stefanie Bartsch, Kenneth C Kirkby, Katrin Bauer, Hubertus Himmerich

Abstract

The interplay between immune and nervous systems plays a pivotal role in the pathophysiology of depression. In depressive episodes, patients show increased production of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. There is limited information on the effect of antidepressant drugs on cytokines, most studies report on a limited sample of cytokines and none have reported effects on IL-22. We systematically investigated the effect of three antidepressant drugs, citalopram, escitalopram and mirtazapine, on secretion of cytokines IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22 and TNF-α in a whole blood assay in vitro, using murine anti-human CD3 monoclonal antibody OKT3, and 5C3 monoclonal antibody against CD40, to stimulate T and B cells respectively. Citalopram increased production of IL-1β, IL-6, TNF-α and IL-22. Mirtazapine increased IL-1β, TNF-α and IL-22. Escitalopram decreased IL-17 levels. The influence of antidepressants on IL-2 and IL-4 levels was not significant for all three drugs. Compared to escitalopram, citalopram led to higher levels of IL-1β, IL-6, IL-17 and IL-22; and mirtazapine to higher levels of IL-1β, IL-17, IL-22 and TNF-α. Mirtazapine and citalopram increased IL-22 production. The differing profile of cytokine production may relate to differences in therapeutic effects, risk of relapse and side effects.

Figures

Figure 1
Figure 1
Mean concentrations (ng/mL) of IL-1ß, IL-6, IL-22 and TNF-α ± standard error (SE) for OKT3/5C3-stimulated blood without (w/o) or with (w) citalopram supplementation using the 1-fold maximum therapeutic concentration of 130 ng/mL.

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