Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms

Abstract 

Immunotherapy with interferon-alpha (IFNα) may induce depressive symptoms, anxiety and major depression when administered for at least 1–3 months at a dose of 3–10 MUI daily, twice or three times a week. Previously, it has been shown that immunotherapy with interleukin-2 (IL-2) significantly induces the cytokine network, as measured by increases in serum IL-6, IL-10 and the IL-2 receptor (IL-2R), and that the immunotherapy-induced changes in the cytokine network are significantly correlated with the increases in depression ratings. The main aim of this study was to examine the effects of immunotherapy with IFNα on the cytokine network in relation to changes in depression and anxiety ratings. Fourteen patients, affected by chronic active C-hepatitis, were treated with IFNα (3–6 MUI s.c. three/six times a week for 6 months) and had measurements of serum IFN-gamma (IFNγ), IL-2, IL-6, IL-6R, IL-8 and IL-10 before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFNα. Severity of depression and anxiety were measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Repeated measure (RM) design ANOVAs showed significantly higher MADRS and HAM-A scores 2–4 weeks and 4–6 months after starting IFNα-based immunotherapy than at baseline. RM design ANOVAs showed significantly higher serum IL-6 and IL-8 levels 2–4 weeks after starting IFNα-based immunotherapy and higher serum IL-10 levels 2–4 weeks and 4–6 months after starting therapy than at baseline. There were significant relationships between the IFNα-induced changes in serum IL-6 or IL-8 and the depression and anxiety scores. The findings show that IFNα-based immunotherapy induces the cytokine network and that IFNα-induced increases in IL-6 predicts the development of depressive symptoms. Depressive symptoms following IFNα treatment may be secondary to cytokine induction, including that of IL-6.

Keywords: Interferon-alpha, Immunotherapy, Cytokines, Depression, Anxiety, Interleukin-6, Hepatitis C