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

279 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    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, 3(10), 1124-1128. https://doi.org/10.1038/nm1097-1124