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09:18
Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Interleukin-15 protects from lethal apoptosis in vivo
S Bulfone-Paus1, D Ungureanu, T Pohl
1Institute of Immunology, Benjamin Franklin Medical Center, Free University Berlin, Germany. bulfone@zedat.fu-berlin.de
Nature Medicine
|October 23, 1997
Summary
Interleukin-15 (IL-15) inhibits apoptosis in T and B cells through RNA-dependent pathways. This cytokine demonstrates potent anti-apoptotic effects in vitro and in vivo, suggesting significant therapeutic potential.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Interleukin-15 (IL-15) shares signaling pathways with Interleukin-2 (IL-2) via the IL-2 receptor beta and gamma chains.
- Despite shared pathways, IL-15 and IL-2 exhibit distinct expression, secretion, target cell ranges, and functional activities, potentially including differential effects on apoptosis.
- While IL-2 can induce or inhibit T-cell apoptosis, IL-15 has been shown to inhibit cytokine deprivation-induced apoptosis in activated T cells.
Purpose of the Study:
- To investigate the mechanisms by which IL-15 modulates distinct apoptosis pathways.
- To determine if IL-15 acts as a general inhibitor of apoptosis in various cellular contexts.
- To evaluate the therapeutic potential of IL-15 as an anti-apoptotic agent.
Main Methods:
- In vitro studies assessed the effect of IL-15 on apoptosis induced by anti-Fas, anti-CD3, dexamethasone, and anti-IgM in activated human T and B cells.
- RNA synthesis dependence was evaluated for IL-15's anti-apoptotic effects.
- In vivo studies utilized a novel IL-15-IgG2b fusion protein to assess the suppression of anti-Fas-induced lethal apoptosis in mice.
Main Results:
- IL-15 significantly inhibited apoptosis induced by multiple stimuli in activated human T and B cells in vitro, an effect dependent on RNA synthesis.
- A novel IL-15-IgG2b fusion protein suppressed lethal, multisystem apoptosis induced by anti-Fas in vivo.
- IL-15, but not IL-2, provided complete protection against lethal hepatic failure in vivo.
Conclusions:
- IL-15 is a potent and general inhibitor of apoptosis across various in vitro and in vivo models.
- The anti-apoptotic activity of IL-15 is dependent on RNA synthesis.
- IL-15 exhibits significant therapeutic potential for conditions involving excessive apoptosis, particularly in hepatic failure.
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