Role of soluble inflammatory mediators and different immune cell populations in early control of symptomatic acute hepatitis C virus infection

J Viral Hepat. 2019 Apr;26(4):466-475. doi: 10.1111/jvh.13050. Epub 2019 Feb 1.

Abstract

The natural course of acute Hepatitis C Virus (aHCV) infection is highly heterogeneous, and only few biomarkers have been identified to reliably predict the outcome of infection. We analysed a large panel of soluble inflammatory mediators, immune cell frequencies and phenotypes using peripheral blood samples from 26 patients with symptomatic aHCV infection from a controlled randomized clinical trial (ISRCTN88729946, www.isrctn.com). We found that patients with a spontaneous early HCV control demonstrated a distinct expression pattern of various soluble immune mediators including IFNα and IL-16. Immune cell phenotype and frequency differed between patients who cleared the viral infection early (n=13) and those who remained HCV RNA positive after 12 weeks of observation (n=13) with a reduced ratio of CD4+ T cells to NK cells in the non-early clearer. Further, correlation analyses of 50 cytokines and chemokines revealed more positive correlations in between the distinct cytokines, especially for IFNα and IL-16, and between the cytokines and HCV RNA levels in spontaneous early clearer patients. Beyond that, in vitro stimulation of CD4+ T cells with IL-16 reduced the susceptibility of these cells to killing by IFNα-activated NK cells. These data indicate that the immune cell composition and cytokine pattern varies considerably in patients with symptomatic aHCV infection. NK cell-mediated killing of CD4+ T cells might affect early control of HCV infection.

Keywords: CD4+ T cells; IFNα; IL-16; NK cells; acute hepatitis C; cytokines; cytotoxicity; immune regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology*
  • Cytotoxicity, Immunologic
  • Female
  • Hepacivirus / genetics
  • Hepacivirus / physiology
  • Hepatitis C / blood*
  • Humans
  • Inflammation Mediators / blood*
  • Interferon-alpha / blood
  • Interleukin-16 / blood
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology*
  • Lymphocyte Count
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Randomized Controlled Trials as Topic
  • Young Adult

Substances

  • Biomarkers
  • Il16 protein, human
  • Inflammation Mediators
  • Interferon-alpha
  • Interleukin-16
  • RNA, Viral