Interleukin 18 -: Interferon γ 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, non 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-1 beta, 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-1 beta, IGIF is processed by the cysteine proteases belonging to caspase family, especially by ICE (interleukin 1 beta concerting 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. (C) 2000 Academic Press.