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

Disclosures

J Viral Hepat. 2008;15(5):331-338. 

In This Article

Summary and Introduction

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-χ, 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.

Hepatitis C virus (HCV) infection has been identified as a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients.[1,2,3] HCV/HIV co-infected patients demonstrate accelerated fibrogenesis leading to more rapid progression to end-stage liver disease in comparison with HCV mono-infected patients.[4,5,6] Several epidemiologic studies have reported that patients with CD4+ lymphopenia, especially <200 CD4+ cells/mm3, have accelerated fibrogenesis[5,7,8,9] and increased intrahepatic inflammation.[8] Although inflammation may promote fibrogenesis through cytokine production,[10,11] few studies have evaluated differences in intrahepatic inflammatory cytokines and cellular inflammation in HCV/HIV co-infected compared with mono-infected patients. While prior studies have observed altered cytokine mRNA levels in co-infected patients,[12,13,14] data are limited on intrahepatic levels of inflammatory cytokines in immunodeficient co-infected patients.

In a previous study, we used immunohistochemistry to enumerate intrahepatic inflammatory cells in co- and mono-infected patients. We noted decreased numbers of intrahepatic CD4+ cells in co-infected compared with mono-infected patients.[15] In peripheral blood, severe lymphopenia (<300 CD4+ cells/mm3) is associated with diminished HCV-specific CD4+ cells.[16] In addition, decreased intrahepatic HCV-specific, CD4+ interferon (IFN)-γ secretion has been associated with accelerated fibrogenesis.[17,18] However, neither the number nor the function of intrahepatic HCV-specific CD4+ cells has been assessed in severely immunodeficient co-infected patients. In the present study, we investigated whether severe immune deficiency in co-infection is associated with changes in intrahepatic inflammatory cytokine mRNA levels. We assessed cytokine levels by real-time PCR performed on liver samples from HCV/HIV co-infected and HCV mono-infected patients.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....