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 IFNalpha, IFNgamma, TNFalpha, TGFbeta(1), IL-2, IL-4, IL-8, IL-10, and IL-12p40. Positive- and negative-strand HCV RNA levels were quantified using a molecular 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 significantly different between the two groups. Detection rates of cytokine mRNAs were lower for the HCV/HIV co-infected group compared to the HCV mono-infected group; the detection rates for TNFalpha, IL-8, and IL-10 were statistically significant. Overall, cytokine mRNA quantities were lower for HCV/HIV co-infected compared to HCV mono-infected persons, with the exception of TGFbeta1. These data suggest that a defect in cytokine activation may occur in HCV/HIV co-infected persons that limits efficient clearance of HCV from the liver.
Blackard
Jason T
JT
Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Komurian-Pradel
Florence
F
Perret
Magali
M
Sodoyer
Mireille
M
Smeaton
Laura
L
St Clair
J Benjamin
JB
Chapman
Stacey
S
Taylor
Lynn E
LE
Paranhos-Baccalà
Glaucia
G
Chung
Raymond T
RT
D001706:Biopsy; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D016209:Interleukin-8; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10