1. Monocyte Activation by Interferon α Is Associated With Failure to Achieve a Sustained Virologic Response After Treatment for Hepatitis C Virus Infection
- Author
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Hartigan-O'Connor, Dennis J, Lin, Din, Ryan, James C, Shvachko, Valentina A, Cozen, Myrna L, Segal, Mark R, Terrault, Norah A, Lanier, Lewis L, Manos, M Michele, and McCune, Joseph M
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,Hepatitis - C ,Liver Disease ,Clinical Research ,Chronic Liver Disease and Cirrhosis ,Digestive Diseases ,Emerging Infectious Diseases ,Hepatitis ,Inflammatory and immune system ,Infection ,Good Health and Well Being ,Adult ,Antigen-Presenting Cells ,Antiviral Agents ,Case-Control Studies ,Cohort Studies ,Dendritic Cells ,Female ,Hepatitis C ,Humans ,Interferon alpha-2 ,Interferon-alpha ,Male ,Middle Aged ,Monocytes ,Polyethylene Glycols ,Recombinant Proteins ,Retrospective Studies ,Ribavirin ,hepatitis C virus ,interferon-alpha ,monocytes ,activation ,dendritic cells ,sustained virologic response ,treatment ,ribavirin ,Toll-like receptor 2 ,interferon-α ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundInterferon 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.MethodsWe 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.ResultsWe 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.ConclusionsThese 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.
- Published
- 2014