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

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 2008
Externally publishedYes

Fingerprint

Virus Diseases
Coinfection
Hepacivirus
HIV
Cytokines
Interferons
Messenger RNA
Liver
Interleukins
CD4 Lymphocyte Count
Interleukin-4
Interleukin-10
Lymphopenia
Transforming Growth Factors
Real-Time Polymerase Chain Reaction
Epidemiologic Studies
Tumor Necrosis Factor-alpha

Keywords

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

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology

Cite this

Hepatic inflammatory cytokine mRNA expression in hepatitis C virus-human immunodeficiency virus co-infection. / Gonzalez, S. A.; Zhang, C.; Fiel, M. I.; Chung, Sun M.; Zhang, L.; Jacobson, I. M.; Talal, A. H.

In: Journal of Viral Hepatitis, Vol. 15, No. 5, 05.2008, p. 331-338.

Research output: Contribution to journalArticle

Gonzalez, S. A. ; Zhang, C. ; Fiel, M. I. ; Chung, Sun M. ; Zhang, L. ; Jacobson, I. M. ; Talal, A. H. / Hepatic inflammatory cytokine mRNA expression in hepatitis C virus-human immunodeficiency virus co-infection. In: Journal of Viral Hepatitis. 2008 ; Vol. 15, No. 5. pp. 331-338.
@article{be39284f02da467a8292a729b18c325e,
title = "Hepatic inflammatory cytokine mRNA expression in hepatitis C virus-human immunodeficiency virus co-infection",
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.",
keywords = "HCV/HIV co-infection, Hepatic cytokines, Hepatic fibrosis, Hepatic inflammation",
author = "Gonzalez, {S. A.} and C. Zhang and Fiel, {M. I.} and Chung, {Sun M.} and L. Zhang and Jacobson, {I. M.} and Talal, {A. H.}",
year = "2008",
month = "5",
doi = "10.1111/j.1365-2893.2007.00949.x",
language = "English (US)",
volume = "15",
pages = "331--338",
journal = "Journal of Viral Hepatitis",
issn = "1352-0504",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Hepatic inflammatory cytokine mRNA expression in hepatitis C virus-human immunodeficiency virus co-infection

AU - Gonzalez, S. A.

AU - Zhang, C.

AU - Fiel, M. I.

AU - Chung, Sun M.

AU - Zhang, L.

AU - Jacobson, I. M.

AU - Talal, A. H.

PY - 2008/5

Y1 - 2008/5

N2 - 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.

AB - 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.

KW - HCV/HIV co-infection

KW - Hepatic cytokines

KW - Hepatic fibrosis

KW - Hepatic inflammation

UR - http://www.scopus.com/inward/record.url?scp=41549149574&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41549149574&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2893.2007.00949.x

DO - 10.1111/j.1365-2893.2007.00949.x

M3 - Article

VL - 15

SP - 331

EP - 338

JO - Journal of Viral Hepatitis

JF - Journal of Viral Hepatitis

SN - 1352-0504

IS - 5

ER -