IFN-γ Reduction by Tricyclic Antidepressants

Abstract

Objective: A growing body of data indicates that an activation of proinflammatory cytokines such as interferon-gamma (IFN-γ) is involved in the pathophysiology of depression and that the suppression of pro-inflammatory cytokine production by antidepressants may lead to an improvement of depressive symptoms. However, the influence of the serotonin and noradrenalin reuptake inhibitor (SNRI) venlafaxine and its metabolite O-desmethylvenlafaxine on the stimulated blood cell secretion of IFN-γ has not been studied so far. Method: We measured IFN-γ levels in the stimulated blood of healthy female subjects in a whole blood assay using the toxic shock syndrome toxin TSST-1 as stimulant. Blood was either supplemented with antidepressants or not. Results: Mean IFN-γ concentrations differed between blood with and without antidepressant supplements ( p = 0.026). Planned contrasts revealed that compared to non-supplemented blood, four of the blood samples supplemented with the tricyclic antidepressants (TCAs) reduced IFN-γ levels: amitriptyline (adjusted p-value ( p = 0.004), nortriptyline ( p = 0.037), imipramine ( p = 0.021), and desipramine ( p = 0.048). There was no significant difference between the control condition and the venlafaxine or O-desmethylvenlafaxine condition. Conclusions: TCAs might, among other mechanisms, act as antidepressants by suppressing the production of pro-inflammatory cytokines, whereas no significant effect of venlafaxine and O-desmethylvenlafaxine on IFN-γ secretion could be demonstrated.