title: Intrahepatic mRNA expression in hepatitis C virus and HIV/hepatitis C virus co-infection: infiltrating cells, cytokines, and influence of HAART.
abstract: OBJECTIVE
  Liver disease is more progressive in HIV/hepatitis C virus (HCV) co-infection than in HCV infection alone. This accelerated pathogenesis is probably influenced by differences in the composition of infiltrating inflammatory cells and the local release of inflammatory and profibrogenic cytokines.
  
  
  METHODS
  Using quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) we studied intrahepatic messenger RNA levels of cytokines and cellular markers defining distinct subsets of inflammatory cells in liver biopsies from 33 HCV-mono-infected and 40 HIV/HCV-co-infected patients.
  
  
  RESULTS
  Despite their well preserved peripheral blood CD4 cell counts (median 598 cells/microl), HIV/HCV-co-infected patients displayed significantly lower CD4 mRNA levels than HCV-mono-infected patients, whereas increased mRNA levels of CD3epsilon, TCRalpha, CD8alpha and CD8beta suggested intrahepatic enrichment of CD8 T cells in HIV co-infection. Intrahepatic mRNA levels of the inflammatory cytokines interferon gamma (IFN-gamma), regulated upon activation, normal T-cell expressed and secreted (RANTES, CCL5), macrophage inflammatory protein 1 alpha (CCL3) and interferon-inducible protein 10 (CXCL10) were significantly higher in HIV-positive than in HIV-negative patients, whereas mRNA levels of the profibrogenic cytokines macrophage chemoattractant protein 1 (CCL2), secondary lymphochemokine (CCL21) and stroma-derived factor 1 (CXCL12) did not differ between the two groups. All changes were less pronounced in the subgroup of HIV-positive patients receiving antiretroviral treatment (HAART) than in untreated HIV-positive patients.
  
  
  CONCLUSIONS
  The accelerated liver disease observed in HIV/HCV-co-infected patients might reflect enhanced intrahepatic inflammatory responses rather than increased local transcription of directly profibrogenic cytokines.
authors: Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA. tkuntzen@partners.org
authors: Thomas
authors: T
authors: Kuntzen
authors: Cristina
authors: C
authors: Tural
authors: Bin
authors: B
authors: Li
authors: Georg
authors: G
authors: Feldmann
authors: Bernd
authors: B
authors: Kupfer
authors: Hans Dieter
authors: HD
authors: Nischalke
authors: Bonaventura
authors: B
authors: Clotet
authors: Tilman
authors: T
authors: Sauerbruch
authors: Juergen K
authors: JK
authors: Rockstroh
authors: Ulrich
authors: U
authors: Spengler
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018946:Chemokine CCL5 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D006526:Hepatitis C / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D018946:Chemokine CCL5; D016207:Cytokines; D012333:RNA, Messenger; D007371:Interferon-gamma