title: Hepatitis C virus genotype and HIV coinfection affect cytokine mRNA levels in unstimulated PBMC but do not shift the T1/T2 balance.
abstract: Rapid progression of hepatitis C virus (HCV) disease in patients with HIV/HCV may reflect different cytokine responses and be influenced by HCV genotype. This is addressed by a study of patients with HIV/HCV coinfection and infection with HCV genotype 2 or 3 (2/3). They are compared with coinfected patients infected with genotype 1 and HCV monoinfected patients matched for HCV genotype. IFN-gamma, IL-10, IL-4 and IL-4delta2 mRNA were quantified by real-time PCR in unstimulated PBMC and after in vitro stimulation with HCV core or nonstructural 3/4A antigen. In unstimulated PBMC, levels of IFN-gamma and IL-4 mRNA were lowest in HIV/HCV genotype 1 patients, intermediate in HIV/HCV genotype 2/3 patients and highest in HCV genotype 2/3 patients. Neither HCV genotype nor HIV affected levels of IL-10 mRNA in unstimulated PBMC or IFN-gamma, IL-4 and IL-10 mRNA in PBMC stimulated with HCV antigens. Levels of IL-4 and IL-4delta2 mRNA correlated in mitogen-stimulated PBMC from all patient groups but both were low in HIV/HCV genotype 1 patients. Serum soluble CD30 levels (a putative marker of a T2 cytokine environment) did not differ between patient groups. The data do not suggest a shift in the T1/T2 balance driven by HIV coinfection or HCV genotype but either may affect IL-4 bioavailability.
authors.affiliation: Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, Western Australia, Australia. lees06@cyllene.uwa.edu.au
authors.forename: Silvia
authors.initials: S
authors.lastname: Lee
authors.forename: Mark W
authors.initials: MW
authors.lastname: Watson
authors.forename: Ben
authors.initials: B
authors.lastname: Clark
authors.forename: James P
authors.initials: JP
authors.lastname: Flexman
authors.forename: Wendy
authors.initials: W
authors.lastname: Cheng
authors.forename: Martyn A H
authors.initials: MA
authors.lastname: French
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
mesh_terms: D000328:Adult; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D005838:Genotype; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000821:virology; D018936:Hepatitis C Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D018936:Hepatitis C Antigens; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma