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J Infect Dis. 2014 May 15;209(10):1602-12. doi: 10.1093/infdis/jit801. Epub 2013 Dec 10.

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

Author information

1
Division of Experimental Medicine.

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.

KEYWORDS:

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

PMID:
24325966
PMCID:
PMC3997582
DOI:
10.1093/infdis/jit801
[Indexed for MEDLINE]
Free PMC Article

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