Interleukin-15 protects from lethal apoptosis in vivo

Silvia Bulfone-Paus, Daniela Ungureanu, Thomas Pohl, Gerd Lindner, Ralf Paus, René Rückert, Hans Krause, Ulrich Kunzendorf

Research output: Contribution to journalArticle

278 Citations (Scopus)

Abstract

Interleukin-15 shares many biological activities with IL-2 and signals through the IL-2 receptor β and γ, chains. However, IL-15 and IL-2 differ in their controls of expression and secretion, their range of target cells and their functional activities. These dissimilarities may include differential effects on apoptosis. For example, IL-2 induces or inhibits T- cell apoptosis in vitro, depending on T-cell activation, whereas IL-15 inhibits cytokine deprivation-induced apoptosis in activated T cells. Studying whether and how IL-15 modulates distinct apoptosis pathways, we show here that apoptosis induced by anti-Fas, anti-CD3, dexamethasone, and/or anti-IgM in activated human T and B cells in vitro is inhibited by IL-15 in a manner dependent on RNA synthesis. In vivo, anti-Fas-induced lethal multisystem apoptosis in mice is suppressed by a novel IL-15-IgG2b fusion protein. Only IL-15, but not IL-2, completely protected from lethal hepatic failure. Thus, IL-15 is a potent, general inhibitor of apoptosis in vitro and in vivo with intriguing therapeutic potential.

Original languageEnglish (US)
Pages (from-to)1124-1128
Number of pages5
JournalNature Medicine
Volume3
Issue number10
DOIs
StatePublished - Oct 1 1997
Externally publishedYes

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Interleukin-15
Apoptosis
Interleukin-2
T-cells
T-Lymphocytes
Interleukin-2 Receptors
Liver Failure
Bioactivity
Dexamethasone
B-Lymphocytes
Fusion reactions
Chemical activation
Cells
RNA
Cytokines

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Bulfone-Paus, S., Ungureanu, D., Pohl, T., Lindner, G., Paus, R., Rückert, R., ... Kunzendorf, U. (1997). Interleukin-15 protects from lethal apoptosis in vivo. Nature Medicine, 3(10), 1124-1128. https://doi.org/10.1038/nm1097-1124

Interleukin-15 protects from lethal apoptosis in vivo. / Bulfone-Paus, Silvia; Ungureanu, Daniela; Pohl, Thomas; Lindner, Gerd; Paus, Ralf; Rückert, René; Krause, Hans; Kunzendorf, Ulrich.

In: Nature Medicine, Vol. 3, No. 10, 01.10.1997, p. 1124-1128.

Research output: Contribution to journalArticle

Bulfone-Paus, S, Ungureanu, D, Pohl, T, Lindner, G, Paus, R, Rückert, R, Krause, H & Kunzendorf, U 1997, 'Interleukin-15 protects from lethal apoptosis in vivo', Nature Medicine, vol. 3, no. 10, pp. 1124-1128. https://doi.org/10.1038/nm1097-1124
Bulfone-Paus S, Ungureanu D, Pohl T, Lindner G, Paus R, Rückert R et al. Interleukin-15 protects from lethal apoptosis in vivo. Nature Medicine. 1997 Oct 1;3(10):1124-1128. https://doi.org/10.1038/nm1097-1124
Bulfone-Paus, Silvia ; Ungureanu, Daniela ; Pohl, Thomas ; Lindner, Gerd ; Paus, Ralf ; Rückert, René ; Krause, Hans ; Kunzendorf, Ulrich. / Interleukin-15 protects from lethal apoptosis in vivo. In: Nature Medicine. 1997 ; Vol. 3, No. 10. pp. 1124-1128.
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