Impact of Steroids on Natural Killer Cells Against Cytotoxicity and Hepatitis C Virus Replication

M Ohira1, S Nishida2, P Tryphonopoulos2

  • 1Department of Surgery, Division of Liver and Gastrointestinal Transplantation, University of Miami Miller School of Medicine, Miami, Florida; Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.

Abstract

Insights

Immunosuppressive drugs impact natural killer (NK) cell functions. Corticosteroids significantly inhibit NK cell proliferation, cytotoxicity, and anti-hepatitis C virus (HCV) activity, unlike other tested immunosuppressants.

Area of Science:

  • Immunology
  • Transplantation Medicine
  • Virology

Background:

  • Natural killer (NK) cells are crucial for eliminating tumor and virus-infected cells.
  • Immunosuppression post-transplantation may increase risks of tumor recurrence and viral infections.
  • The precise impact of immunosuppressive drugs on NK cell function remains unclear.

Purpose of the Study:

  • To investigate the effects of common immunosuppressive drugs on NK cell functions.
  • To determine how immunosuppression influences NK cell-mediated anti-tumor and anti-viral activities.

Main Methods:

  • NK cells were cultured with interleukin-2 and various immunosuppressive drugs (tacrolimus, cyclosporine A, methylprednisolone [MP], mycophenolate mofetil, rapamycin).
  • Assessed NK cell phenotype, proliferation, cytotoxicity against K562 cells, cytokine production, and anti-hepatitis C virus (HCV) activity.
  • Utilized HCV genomic replicon cells to evaluate anti-viral effects.

Main Results:

  • Tacrolimus and cyclosporine A demonstrated minimal impact on NK cell functions.
  • Mycophenolate mofetil and rapamycin primarily inhibited NK cell proliferation.
  • Methylprednisolone (MP) significantly impaired NK cell proliferation, cytotoxicity, and anti-HCV activity, also reducing activation markers and interferon-γ production.

Conclusions:

  • Corticosteroids, specifically MP, exert distinct and significant inhibitory effects on NK cell functions.
  • These findings highlight the critical implications of corticosteroid use on NK cell-mediated cytotoxicity and anti-HCV responses in transplant recipients.

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