Hepatic inflammatory cytokine mRNA expression in hepatitis C virus-human immunodeficiency virus co-infection

S. A. Gonzalez, C. Zhang, M. I. Fiel, S. Chung, L. Zhang, I. M. Jacobson, A. H. Talal

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Although epidemiologic studies have documented that hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infected patients have accelerated fibrogenesis, especially those with CD4+ cell counts <200 cells/mm3, the pathogenic mechanisms are poorly understood. We investigated whether severe immunodeficiency in co-infection is associated with changes in intrahepatic inflammatory cytokine mRNA levels. We measured interferon (IFN)-γ, tumour necrosis factor-α, transforming growth factor (TGF)-β1, interleukin (IL)-4, IL-10, IL-12p35 and IL-12p40 mRNA levels by real-time PCR performed on liver samples from HCV mono-infected (n = 19) and HCV/HIV co-infected (n = 24) patients. Co-infected patients had decreased intrahepatic mRNA levels of IFN-γ (P = 0.09), IL-4 (P = 0.05) and IL-12p35 (P = 0.04) compared with mono-infected patients, while IL-10 was increased (P = 0.07). In co-infected patients, IFN-γ mRNA levels increased linearly with increasing peripheral CD4+ cell counts by 1.23 times relative to the calibrator for every 100 CD4+ cells/mm3 increase (P = 0.02). No other cytokines were significantly associated with CD4+ cell counts. In conclusion, HIV-induced lymphopenia may result in hepatic inflammatory cytokine suppression in HCV/HIV co-infection. Intrahepatic IFN-γ levels are significantly reduced in patients with advanced immunodeficiency. Further studies are needed to assess whether decreased IFN-γ secretion by HCV-specific CD4+ cells may account for accelerated fibrogenesis in these patients.

Original languageEnglish (US)
Pages (from-to)331-338
Number of pages8
JournalJournal of Viral Hepatitis
Volume15
Issue number5
DOIs
StatePublished - May 1 2008
Externally publishedYes

Keywords

  • HCV/HIV co-infection
  • Hepatic cytokines
  • Hepatic fibrosis
  • Hepatic inflammation

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology

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