Pretreatment levels of sTNF-R1 and sIL-6R are associated with a higher vulnerability for IFN-alpha-induced depressive symptoms in patients with malignant melanoma

Immunomodulatory therapy with interferon-alpha (IFN-alpha) often leads to neuropsychiatric side effects, especially depression. An activation of the immune system is discussed to trigger neurotransmitter changes and depressive illness. So far, few data are available about biologic markers, who may predict the individual risk for developing depressive symptoms during IFN-alpha therapy. The aim of the present study was to investigate the predictive role of certain immunologic markers for the development of IFN-alpha-induced depression. We hypothesized that patients characterized by a proinflammatory and TH1-accentuated immune response before treatment might have an increased risk for developing depressive mood changes. Thirty-three melanoma patients were prospectively investigated during adjuvant treatment with IFN-alpha-2a/2b (3 x 3 Mio units/wk). Depressive mood changes were assessed with the self-rating depression scale (SDS, Zung-scale) before and during IFN-alpha treatment. Serum concentrations of soluble tumor necrosis factor-R1 (sTNF-R1), soluble interleukin-6R (sIL-6R), sIL-4R, and neopterin were measured before and after 3 months of treatment. sIL-6R, which was negatively associated with SDS scores, significantly predicted higher depression scores in the first 3 months of IFN-alpha treatment. sTNF-R1, which was positively associated with SDS scores, significantly predicted the development of late depressive symptoms after 6 months of therapy. In contrast to the initial hypothesis, patients characterized by high sTNF-R1 and low sIL-6R baseline levels, indicating an anti-inflammatory condition before therapy, had a higher vulnerability for depression during IFN-alpha therapy.