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IMMUNE CORRELATES OF TREATMENT INDUCED DEPRESSION IN CHRONIC HCV INFECTION
C Krueger1, H Chow2, S Mante2, S Wong2, JD Rempel1,2
1Department of Immunology, 2Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg
Chronic Hepatitis C Virus (cHCV) infection is treated with pegylated interferon-alpha (PEG) and ribavirin. Depression, a serious side-effect, is the main reason for treatment discontinuation. Clinical depression correlates with the presence of pro-inflammatory cytokines IFN-alpha, IL-1beta, IL-6 and TNF-alpha and a decline in the anti-inflammatory cytokine IL-10. The purpose of this research is to determine whether the balance of cytokine activity at baseline (pre-treatment) can predict treatment-induced depression. Cytokine activity was evaluated by the in vitro culture of peripheral blood mononuclear cells (PBMC) with PEG alone or with HCV proteins Core and NS3. Supernatant cytokine concentrations, evaluated by ELISA, were analyzed against whether the individual experienced an increase in depression scores (IDS) following treatment or not (NDS). Culture with PEG alone, resulted in a 3 and 11 fold elevation in IL-6 and IL-1beta synthesis respectively in the IDS cohort (n=6) over the NDS cohort (n=6). These cytokines were further upregulated with the addition of Core and NS3 to cell culture. In contrast, Core and NS3 predominately enhanced IL-10 production in the NDS cohort. Similar patterns in cytokine synthesis were noted upon culture of cells with ribavirin. To date, these data suggest that an increase in the balance of pro-inflammatory over anti-inflammatory cytokine activity at baseline is associated with increased depression scores during treatment. In this ongoing study, cytokine mRNA expression during treatment is also being examined. Being able to predict IFN-alpha induced depression in individuals with a cHCV infection will lead to better management of side effects and improved treatment outcomes.