IL-15 protects intestinal epithelial cells

Eur J Immunol. 2006 Oct;36(10):2691-9. doi: 10.1002/eji.200535173.


IL-15, a T-cell growth factor, has been shown to be increased in inflammatory bowel disease (IBD). It has been suggested that neutralization of IL-15 could protect from T cell-dependent autoimmune inflammation. On the other hand, an anti-apoptotic effect of IL-15 has been demonstrated in kidney epithelial cells during nephritis. We therefore tested the role of IL-15 in two different experimental models of colitis in vivo, and in models of intestinal epithelial cell (IEC) apoptosis in vitro. IL-15 blockade in chronic dextran sulphate sodium-induced colitis resulted in aggravation of the disease with a significantly 2.1-fold increased epithelial damage score compared to controls. TUNEL staining clearly revealed increased apoptosis. IL-6, TNF and IFN-gamma secretion by mesenteric lymph node cells were increased. In the T cell-dependent SCID transfer model of colitis IL-15 neutralization reduced the inflammatory infiltration and proinflammatory cytokine production. Despite that, the intestinal epithelial damage was not reduced. In vitro, IL-15 pre-incubation prevented up to 75% of CH11 antibody-induced apoptosis in SW-480 cells and reduced caspase-3 activity. According to this, endogenously produced IL-15 in chronic colitis does not only act as a proinflammatory cytokine but has at the same time the potential to reduce mucosal damage by preventing IEC apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Line
  • Colitis / immunology*
  • Colitis / pathology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • In Situ Nick-End Labeling
  • Interferon-gamma / metabolism
  • Interleukin-15 / immunology*
  • Interleukin-6 / metabolism
  • Intestinal Mucosa / immunology*
  • Lymph Nodes / immunology
  • Lymphocyte Activation / immunology
  • Mesentery / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukin-15
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Caspase 3