Journal of Medical Virology 78:202–207 (2006) Intrahepatic Cytokine Expression is Downregulated During HCV/HIV Co-Infection

HIV co-infection is associated with reduced HCV treatment response rates and accelerated HCV-related liver disease. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the roles of HIV and/or its therapies on cytokine expression are unknown. Total RNA was extracted from liver biopsies of 12 HCV mono-infected and 14 HCV/HIV co-infected persons.We used real-time PCR to quantify cytokines that contribute to innate and adaptive immune responses, including IFNa, IFNg, TNFa, TGFb1, IL-2, IL-4, IL-8, IL-10, and IL-12p40. Positive- and negative-strand HCV RNA levels were quantified using amolecular beacon approach. Detection of positive-strand HCV RNA was 100 % in both groups; negative-strand HCV RNA was detected in four (33%) HCV mono-infected persons and in nine (64%) HCV/HIV co-infected persons. Median strand-specific HCV RNA levels were not signifi-cantly different between the two groups. Detec-tion rates of cytokine mRNAs were lower for the HCV/HIV co-infected group compared to the HCV mono-infected group; the detection rates for TNFa, IL-8, and IL-10were statistically significant. Overall, cytokinemRNAquantitieswere lower for HCV/HIV co-infected compared to HCV mono-infected persons, with the exception of TGFb1. These data suggest that a defect in cytokine activation may occur in HCV/HIV co-infected persons that limits efficient clearance ofHCV from the liver. J. Med. Virol. 78:202–207, 2006