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Updated: Oct 4, 2026

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
Activation of caspase-3 by interferon alpha causes interleukin-16 secretion but fails to modulate activation induced
O Ludwiczek1, A Kaser, R O Koch
1Department of Medicine, Division of Gastroenterology and Hepatology, University Hospital Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Abstract:
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.
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