Monocyte activation by interferon α Is associated with failure to achieve a sustained virologic response after treatment for hepatitis c virus infection

Dennis Hartigan-O'Connor, Din Lin, James C. Ryan, Valentina A. Shvachko, Myrna L. Cozen, Mark R. Segal, Norah A. Terrault, Lewis L. Lanier, M. Michele Manos, Joseph M. McCune

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1602-1612
Number of pages11
JournalJournal of Infectious Diseases
Volume209
Issue number10
DOIs
StatePublished - May 15 2014

Fingerprint

Hepatitis Viruses
Virus Diseases
Interferons
Monocytes
Hepacivirus
Ribavirin
Antigen-Presenting Cells
Dendritic Cells
Therapeutics
Poisons
Myeloid Cells
Antiviral Agents
Leukocytes
Genotype
Sustained Virologic Response
Cytokines
Pharmaceutical Preparations

Keywords

  • activation
  • dendritic cells
  • hepatitis C virus
  • interferon
  • monocytes
  • ribavirin
  • sustained virologic response
  • Toll-like receptor 2
  • treatment

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Monocyte activation by interferon α Is associated with failure to achieve a sustained virologic response after treatment for hepatitis c virus infection. / Hartigan-O'Connor, Dennis; Lin, Din; Ryan, James C.; Shvachko, Valentina A.; Cozen, Myrna L.; Segal, Mark R.; Terrault, Norah A.; Lanier, Lewis L.; Manos, M. Michele; McCune, Joseph M.

In: Journal of Infectious Diseases, Vol. 209, No. 10, 15.05.2014, p. 1602-1612.

Research output: Contribution to journalArticle

Hartigan-O'Connor, Dennis ; Lin, Din ; Ryan, James C. ; Shvachko, Valentina A. ; Cozen, Myrna L. ; Segal, Mark R. ; Terrault, Norah A. ; Lanier, Lewis L. ; Manos, M. Michele ; McCune, Joseph M. / Monocyte activation by interferon α Is associated with failure to achieve a sustained virologic response after treatment for hepatitis c virus infection. In: Journal of Infectious Diseases. 2014 ; Vol. 209, No. 10. pp. 1602-1612.
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AU - Cozen, Myrna L.

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AB - 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.

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