Interleukin 18--interferon gamma inducing factor--a novel player in tumour immunotherapy?

Cytokine. 2000 Apr;12(4):332-8. doi: 10.1006/cyto.1999.0563.

Abstract

The list of interleukins is growing at a steady rate. Although, it is over 8 years since the initial description of interferon gamma inducing factor (IGIF, now called IL-18), this novel cytokine is still not well characterised. However, the data were sufficient to support the testing of IL-18 in experimental tumour therapy. IL-18 is produced mainly by macrophages. Similarly to IL-1beta, IL-18 does not possess a signal sequence allowing direct secretion through the plasma membrane. Although, the exact mechanism of IL-18 secretion is not confirmed, it seems that, like IL-1beta, IGIF is processed by the cysteine proteases belonging to caspase family, especially by ICE (interleukin 1beta converting enzyme). Among the target cells responding to IL-18 are T lymphocytes and NK cells, which, under the influence of IL-18, produce substantial amounts of IFN-gamma. In this respect IL-18 seems to be even stronger than IL-12. Similarly to IL-12, IL-18 stimulates cytotoxicity of T and NK cells. Moreover, it enhances FasL-mediated cytotoxicity of CD4+ T and NK cells. A potential role of IL-18 in tumour immunotherapy is discussed in this article with special emphasis on the similarities with IL-12 and the potential mechanisms of its antitumour activity in preclinical models in mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cloning, Molecular
  • Drug Synergism
  • Humans
  • Immunotherapy / methods
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology
  • Interleukin-18 / pharmacology
  • Interleukin-18 / therapeutic use*
  • Interleukin-18 Receptor alpha Subunit
  • Mice
  • Neoplasms / therapy*
  • Receptors, Interleukin / immunology
  • Receptors, Interleukin-18
  • Signal Transduction / immunology

Substances

  • IL18R1 protein, human
  • Il18r1 protein, mouse
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-18