Interferon-lambda serum levels in hepatitis C

J Hepatol. 2011 May;54(5):859-65. doi: 10.1016/j.jhep.2010.08.020. Epub 2010 Oct 23.


Background & aims: Dendritic cells (DCs) trigger adaptive immune responses and are an important source of antiviral cytokines. In hepatitis C virus (HCV) infection DC function is markedly impaired. Thus far, studies have focused on types I and II interferon (IFN). We studied IFN-lambda1 (IL-29) and IFN-lambda2/3 (IL-28A/B) serum levels in patients with different outcomes of HCV infection.

Methods: IFN-lambdas were measured by ELISAs detecting IL-29 or IL-28A and IL-28B, respectively. Results were stratified with respect to the recently discovered rs12979860 T/C polymorphism upstream of the IL-28B gene.

Results: In general IL-29 serum levels exceeded IL-28A/B at least twofold, with IL-29 and IL-28A/B levels being significantly higher in carriers of the rs12979860 C allele than in TT homozygous individuals (p<0.02). IL-29 levels were substantially lower in patients with chronic hepatitis C than in healthy controls (p=0.005) and patients with spontaneously resolved hepatitis (p=0.001). Patients with acute hepatitis C showed IL-29 levels intermediate between chronic hepatitis C and normal controls; and IL-29 serum levels were higher in patients who spontaneously resolved hepatitis C than in those who became chronic. In vitro HCV proteins NS3 and E2 directly inhibited IL-29 production in poly I:C-stimulated purified DCs.

Conclusions: Our data suggest that HCV proteins modify IFN-lambda production in DCs. Carriers of the rs12979860 C allele associated with resolution of HCV infection exhibited increased IFN-lambda levels. Moreover, high IFN-lambda levels predisposed to spontaneous resolution of HCV infection. Thus, IFN-lambdas seem to play an important role in the control of hepatitis C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / immunology
  • Cross-Sectional Studies
  • Dendritic Cells / immunology
  • Female
  • Genotype
  • Hepacivirus / genetics*
  • Hepacivirus / immunology
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / metabolism*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferons
  • Interleukins* / blood
  • Interleukins* / genetics
  • Interleukins* / immunology
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Prognosis
  • Tetraspanin 28
  • Toll-Like Receptor 2 / immunology
  • Viral Envelope Proteins / genetics
  • Viral Load / immunology
  • Viral Nonstructural Proteins / genetics


  • Antigens, CD
  • CD81 protein, human
  • interferon-lambda, human
  • Interleukins
  • NS3 protein, hepatitis C virus
  • TLR2 protein, human
  • Tetraspanin 28
  • Toll-Like Receptor 2
  • Viral Envelope Proteins
  • Viral Nonstructural Proteins
  • glycoprotein E2, Hepatitis C virus
  • Interferons