Differential expression of toll-like receptor mRNA in treatment non-responders and sustained virologic responders at baseline in patients with chronic hepatitis C

Liver Int. 2006 Nov;26(9):1100-10. doi: 10.1111/j.1478-3231.2006.01357.x.

Abstract

Background/aims: The contribution of the host immune response to sustained virologic response is not clear in patients with chronic hepatitis C (CHC). The aim of this study was to explore the relationship of the toll-like receptor (TLR) expression with the outcome of antiviral therapy in hepatitis C viral infection.

Methods: Peripheral blood mononuclear cells (PBMC) were obtained from 15 CHC patients before a 48-week treatment with pegylated interferon (PEG IFN) alpha-2a and ribavirin. A multiplex semi-quantitative reverse-trancriptase polymerase chain reaction (RT-PCR) was used to compare the relative abundance of TLR2-9 transcripts.

Results: mRNA levels of TLR2, 3 and 6 were significantly higher in CHC subjects compared with normal controls (n=8). When patients were classified into non-responders (n=8) and sustained virological responders (n=7) according to the virological outcome of the treatment, there was a clear difference in baseline mRNA expression of TLRs and T-helper (Th) 1/2 cytokines. In addition, the mRNA expression of IFN-gamma and nuclear factor of activated T cells (NFAT), which is exclusively expressed in activated T cells, was inversely correlated with that of TLR4, 6 and 9 in non-responders.

Conclusions: TLRs mRNA levels are differentially expressed in baseline PBMC of chronic HCV-infected subjects with or without responsiveness to antiviral therapy.

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Cytokines / genetics
  • Drug Therapy, Combination
  • Female
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Interferon-gamma / genetics
  • Male
  • Middle Aged
  • NFATC Transcription Factors / genetics
  • Polyethylene Glycols / therapeutic use
  • RNA, Messenger / blood*
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribavirin / therapeutic use
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism
  • Toll-Like Receptors / genetics*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Cytokines
  • Interferon alpha-2
  • Interferon-alpha
  • NFATC Transcription Factors
  • RNA, Messenger
  • Recombinant Proteins
  • Toll-Like Receptors
  • Polyethylene Glycols
  • Ribavirin
  • Interferon-gamma
  • peginterferon alfa-2a