Interleukin 18--interferon gamma inducing factor--a novel player in tumour immunotherapy?
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.
Gołab
J
J
Department of Immunology, Institute of Biostructure, Medical University of Warsaw, Poland. jgolab@ib.amwaw.edu.pl
D000818:Animals; D003001:Cloning, Molecular; D004357:Drug Synergism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D053727:Interleukin-18 Receptor alpha Subunit; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D018123:Receptors, Interleukin / Q000276:immunology; D053724:Receptors, Interleukin-18; D015398:Signal Transduction / Q000276:immunology
C508572:IL18R1 protein, human; C508573:Il18r1 protein, mouse; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18