title: Interferon-lambda serum levels in hepatitis C.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany. bettina.langhans@ukb.uni-bonn.de
authors.forename: Bettina
authors.initials: B
authors.lastname: Langhans
authors.forename: Bernd
authors.initials: B
authors.lastname: Kupfer
authors.forename: Ingrid
authors.initials: I
authors.lastname: Braunschweiger
authors.forename: Simone
authors.initials: S
authors.lastname: Arndt
authors.forename: Wibke
authors.initials: W
authors.lastname: Schulte
authors.forename: Hans Dieter
authors.initials: HD
authors.lastname: Nischalke
authors.forename: Jacob
authors.initials: J
authors.lastname: Nattermann
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D003430:Cross-Sectional Studies; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000097:blood / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D060225:Tetraspanin 28; D051195:Toll-Like Receptor 2 / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics; D019562:Viral Load / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics; D000095022:Interferon Lambda; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D015703:Antigens, CD; D007372:Interferons; D007378:Interleukins; D060225:Tetraspanin 28; D051195:Toll-Like Receptor 2; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C554798:CD81 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C495342:TLR2 protein, human; C091015:glycoprotein E2, Hepatitis C virus