IFN-gamma reduction by tricyclic antidepressants

A growing body of data indicates that an activation of proinflammatory cytokines such as interferon-gamma (IFN-gamma) 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-gamma has not been studied so far.

We measured IFN-gamma 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.

Mean IFN-gamma 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-gamma 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.

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-gamma secretion could be demonstrated.