title: Persistent pro-inflammatory cytokines following the initiation of pegylated IFN therapy in hepatitis C infection is associated with treatment-induced depression.
abstract: Pegylated interferon (IFN), the basis for chronic hepatitis C virus (HCV) treatment, causes depression in 30-40% of patients. The potential for cytokine mRNA patterns from baseline into early treatment to associate with the onset of treatment-induced depression (TID) was examined. Depression was measured by the Beck Depression Inventory at baseline and weeks 2, 4, 8 and 12 of treatment (n = 38). At baseline and weeks 2 and 4, peripheral blood mononuclear cell (PMBC, n = 28), isolated ex vivo, were examined for tumour neurosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10 mRNA expression. In patients that developed treatment-induced depression, pro-inflammatory TNF-alpha mRNA levels from baseline into week 4 of therapy remained constant (1.1-fold increase); whereas IL-1beta transcripts decreased 3.5 fold. However, corresponding TNF-alpha (3-fold, P < 0.05) and IL-1beta (7.5-fold) transcript expression diminished to a greater extent in the absence of TID. Changes in TNF-alpha mRNA values correlated to the average change in BDI scores over the 12 weeks (r = 0.56, P < 0.05). Concomitantly, anti-inflammatory IL-10 transcript levels decreased in (TID), relative to increased expression in the absence of TID (P < 0.05). The potential influence of IL-10 was observed upon calculation of individual pro- verses anti-inflammatory mRNA ratios. Stable in the presence of depression, TNF-alpha/IL-10 and IL-1beta/IL-10 mRNA ratios declined significantly over time in its absence (P < 0.05). This study suggests that in chronic HCV infection, upon pegylated IFN administration persistent pro-inflammatory cytokine MRNA expression associates with TID. In contrast, therapeutic activation of mechanisms that decrease pro-inflammatory immunity may protect against depression during therapy.
authors.affiliation: Section of Hepatology, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Krueger
authors.forename: K
authors.initials: K
authors.lastname: Hawkins
authors.forename: S
authors.initials: S
authors.lastname: Wong
authors.forename: M W
authors.initials: MW
authors.lastname: Enns
authors.forename: G
authors.initials: G
authors.lastname: Minuk
authors.forename: J D
authors.initials: JD
authors.lastname: Rempel
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003863:Depression / Q000139:chemically induced*; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D016899:Interferon-beta; D007372:Interferons / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D011795:Surveys and Questionnaires
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D016899:Interferon-beta; D007372:Interferons; C417083:peginterferon alfa-2b; C428112:peginterferon beta-1a