Interleukin-15 Protects From Lethal Apoptosis in Vivo

Nat Med. 1997 Oct;3(10):1124-8. doi: 10.1038/nm1097-1124.

Abstract

Interleukin-15 shares many biological activities with IL-2 and signals through the IL-2 receptor beta and gamma 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • CD3 Complex / immunology
  • CD3 Complex / physiology
  • Cells, Cultured
  • DNA Fragmentation
  • Dexamethasone / pharmacology
  • Humans
  • Immunoglobulin G / pharmacology
  • Immunoglobulin M / pharmacology
  • Interleukin-15 / pharmacology*
  • Lymphocyte Activation
  • Mice
  • Palatine Tonsil
  • Recombinant Fusion Proteins / pharmacology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Transcription, Genetic
  • fas Receptor / immunology
  • fas Receptor / physiology

Substances

  • CD3 Complex
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukin-15
  • Recombinant Fusion Proteins
  • fas Receptor
  • Dexamethasone