title: Viral factors associated with cytokine expression during HCV/HIV co-infection.
abstract: Co-infection with human immunodeficiency virus (HIV) is associated with reduced hepatitis C virus (HCV) treatment response and accelerated HCV disease. Cytokines, as mediators of immune responses, inflammation, and fibrogenesis, may underlie important differences in HCV pathogenesis during HIV co-infection. We previously found that serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) increased after HCV therapy with interferon (IFN) in HCV/HIV co-infected patients; however, cytokine levels were not predictive of HCV therapeutic response. Here, we examined viral factors associated with expression of IL-8, TNF-alpha, and transforming growth factor-beta1 (TGF-beta1) in uninfected, HCV mono-infected, HIV mono-infected, and HCV/HIV co-infected persons. HIV co-infection was associated with decreased IL-8 detection but not TNF-alpha detection. A significant interaction effect demonstrated that HIV infection was associated with elevated TGF-beta1 in HCV-positive individuals but not in HCV-negative individuals. The induction of a sustained profibrotic signal, such as TGF-beta1, by HIV may cause accelerated liver fibrosis during HCV/HIV co-infection and may hinder the host's ability to mount an effective HCV-specific immune response. Further studies are warranted to identify noninvasive markers of liver disease for the clinical management of HCV disease, particularly when liver biopsies have not been performed or are contraindicated.
authors.affiliation: Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA
authors.forename: Jason T
authors.initials: JT
authors.lastname: Blackard
authors.forename: Minhee
authors.initials: M
authors.lastname: Kang
authors.forename: J Benjamin
authors.initials: JB
authors.lastname: St Clair
authors.forename: Wenyu
authors.initials: W
authors.lastname: Lin
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kamegaya
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.forename: Margaret James
authors.initials: MJ
authors.lastname: Koziel
authors.forename: Marion G
authors.initials: MG
authors.lastname: Peters
authors.forename: Janet
authors.initials: J
authors.lastname: Andersen
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
mesh_terms: D000328:Adult; D015897:Comorbidity; D016207:Cytokines / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D053773:Transforming Growth Factor beta1 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014780:Viruses / Q000378:metabolism*
chemical_list: D016207:Cytokines; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha