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/mm(3), 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)-gamma, tumour necrosis factor-alpha, transforming growth factor (TGF)-beta(1), 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-gamma (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-gamma mRNA levels increased linearly with increasing peripheral CD4+ cell counts by 1.23 times relative to the calibrator for every 100 CD4+ cells/mm(3) 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-gamma levels are significantly reduced in patients with advanced immunodeficiency. Further studies are needed to assess whether decreased IFN-gamma secretion by HCV-specific CD4+ cells may account for accelerated fibrogenesis in these patients.

• Authors: S A Gonzalez, C Zhang, M I Fiel, S Chung, L Zhang, I M Jacobson, A H Talal
• Journal: Journal of viral hepatitis (J Viral Hepat) Vol. 15 Issue 5 Pg. 331-8 (May 2008) ISSN: 1365-2893 [Electronic] England
• PMID: 18179452 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• RNA, Messenger

Topics

• Adult
• Aged
• CD4 Lymphocyte Count
• Cytokines (biosynthesis, genetics)
• Female
• Gene Expression Profiling
• HIV Infections (complications, immunology)
• Hepatitis C (complications, immunology)
• Humans
• Liver (pathology)
• Male
• Middle Aged
• RNA, Messenger (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction (methods)