Hepatitis delta: In vitro evaluation of cytotoxicity and cytokines involved in PEG-IFN therapy

Int Immunopharmacol. 2021 Feb:91:107302. doi: 10.1016/j.intimp.2020.107302. Epub 2021 Jan 1.

Abstract

The treatment for hepatitis Delta virus (HDV) still consists of Pegylated interferon (PEG-IFN) combined with inhibitors of Hepatitis B virus (HBV) replication. In some patients may be occur a virological response, which means a negative HDV RNA 6 months after stopping treatment. In this study it was conducted an in vitro approach with the aim to mimic possible immunological events that are observed in patients responding to PEG-IFN therapy. Jurkat cells (human T lymphocyte cell line) were employed alone or co-cultured with THP-1 (human monocytic cell line) and stimulated with controls and HBV Surface Antigen (HBsAg), Small-Delta Antigen (SHDAg), and HBsAg + SHDAg combined. Twenty-four hours stimulation with SHDAg and/or HBSAg led to a toxic profile in a co-culture condition and cell supernatants were collected for cytokines quantification. PEG-IFN was added and cells were incubated for additional 24 h. Co-cultured cells incubated with the association (SHDAg + PEG-IFN) significantly produced levels of IFN-γ, IL-2 and IL-12. On the other hand, the HBsAg alone was able to inhibit the production of IFN-γ, suggesting that this antigen may hinder the treatment exclusively with PEG-IFN.

Keywords: Cytokines; HBV; HDV; PEG-IFN.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Coculture Techniques
  • Cytokines / metabolism*
  • Cytotoxicity, Immunologic / drug effects*
  • Hepatitis B Surface Antigens / pharmacology
  • Hepatitis D / drug therapy*
  • Hepatitis D / immunology
  • Hepatitis D / metabolism
  • Hepatitis D / virology
  • Hepatitis Delta Virus / immunology*
  • Hepatitis Delta Virus / pathogenicity
  • Hepatitis delta Antigens / pharmacology
  • Host-Pathogen Interactions
  • Humans
  • Interferon-gamma / metabolism
  • Interferons / pharmacology*
  • Interleukin-12 / metabolism
  • Interleukin-2 / metabolism
  • Jurkat Cells
  • Polyethylene Glycols / pharmacology*
  • Signal Transduction
  • THP-1 Cells

Substances

  • Antiviral Agents
  • Cytokines
  • Hepatitis B Surface Antigens
  • Hepatitis delta Antigens
  • IFNG protein, human
  • IL2 protein, human
  • Interleukin-2
  • Interleukin-12
  • Polyethylene Glycols
  • Interferon-gamma
  • Interferons