title: Monocyte activation by interferon α is associated with failure to achieve a sustained virologic response after treatment for hepatitis C virus infection.
abstract: BACKGROUND
  Interferon α (IFN-α) and ribavirin can induce a sustained virologic response (SVR) in some but not all hepatitis C virus (HCV)-infected patients. The mechanism of effective treatment is unclear. One possibility is that IFN-α differentially improves the functional capacity of classic myeloid dendritic cells (mDCs) by altering expression of surface molecules or cytokines. Others have proposed that antigen-presenting cell activation could be paradoxically detrimental during HCV infection because of the production by monocytes of substances inhibitory or toxic to plasmacytoid dendritic cells.
  
  
  METHODS
  We examined responses to in vitro IFN-α treatment of peripheral blood leukocyte samples from a retrospective treatment cohort of nearly 200 HCV-seropositive patients who had undergone antiviral therapy with ribavirin and pegylated IFN. We analyzed the variable responses of antigen-presenting cell subsets to drug.
  
  
  RESULTS
  We found that patients achieving SVR were no more likely to have robust mDC activation in response to IFN-α than those who did not achieve SVR. Rather, patients achieving SVR were distinguished by restrained monocyte activation in the presence of IFN-α, a factor that was second in importance only to IL28B genotype in its association with SVR.
  
  
  CONCLUSIONS
  These results suggest that interindividual variability in the response of monocytes to IFN-α is an important determinant of treatment success with IFN-α-based regimens.
authors: Division of Experimental Medicine.
authors: Dennis J
authors: DJ
authors: Hartigan-O'Connor
authors: Din
authors: D
authors: Lin
authors: James C
authors: JC
authors: Ryan
authors: Valentina A
authors: VA
authors: Shvachko
authors: Myrna L
authors: ML
authors: Cozen
authors: Mark R
authors: MR
authors: Segal
authors: Norah A
authors: NA
authors: Terrault
authors: Lewis L
authors: LL
authors: Lanier
authors: M Michele
authors: MM
authors: Manos
authors: Joseph M
authors: JM
authors: McCune
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells; D000998:Antiviral Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D015331:Cohort Studies; D003713:Dendritic Cells; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b
keywords: Toll-like receptor 2; activation; dendritic cells; hepatitis C virus; interferon-α; monocytes; ribavirin; sustained virologic response; treatment