Activation of caspase-3 by interferon alpha causes interleukin-16 secretion but fails to modulate activation induced cell death

Eur Cytokine Netw. 2001 Jul-Sep;12(3):478-86.


Interferon alpha (IFN-alpha) is the mainstay in the treatment of chronic hepatitis C virus (HCV) infection. Interleukin-16 (IL-16) attracts CD4+ cells to sites of inflammation and plays a role in the interaction of dendritic cells, T cells and B cells. In this study, we show that IFN-alpha itself induces IL-16 secretion by peripheral blood lymphocytes (PBL) and enhances IL-16 secretion by anti-CD3 stimulated PBL. Pro-IL-16 is cleaved into its active form by caspase-3. IFN-alpha increases caspase-3 mRNA levels in activated T cells (ATC), as shown by Northern blot analysis, whereas IL-16 mRNA levels are not affected by IFN-alpha. IL-16 secretion into culture supernatants correlates tightly with intracellular caspase-3 activity in ATC. In our experiments addition of specific caspase inhibitors did not reduce the proportion of ATC undergoing Fas-mediated cell death, but completely blocked IFN-alpha-induced IL-16 secretion into culture supernatants. In conclusion, our results suggest that IFN-alpha activates caspase-3, thereby increasing secretion of IL-16, whereas IFN-alpha-enhanced Fas-mediated cell death in ATC is not caspase-dependent.

MeSH terms

  • Antibodies / immunology
  • Antibodies / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Blood Cells / drug effects
  • Blood Cells / metabolism
  • CD3 Complex / immunology
  • Caspase 3
  • Caspases / drug effects
  • Caspases / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Interferon-alpha / metabolism*
  • Interferon-alpha / pharmacology
  • Interleukin-16 / antagonists & inhibitors
  • Interleukin-16 / biosynthesis*
  • Interleukin-16 / metabolism
  • RNA, Messenger / metabolism*
  • T-Lymphocytes / metabolism


  • Antibodies
  • CD3 Complex
  • Enzyme Inhibitors
  • Interferon-alpha
  • Interleukin-16
  • RNA, Messenger
  • CASP3 protein, human
  • Caspase 3
  • Caspases