Augmentation by interleukin-18 of MHC-nonrestricted killer activity of human peripheral blood mononuclear cells in response to interleukin-12

Interleukin (IL)-18 is a novel cytokine with pleiotropic functions. In the present study, we examined the induction of the killer activity of peripher al blood mononuclear cells (MNC:) against lung cancer cell lines upon treat ment with IL-18 in combination with IL-12. Cytotoxic activity was measured by standard Cr-51 release assay. IL-18 (100 ng/ml) was found to significant ly augment IL-12-induced killer activity in a MHC-nonrestricted manner agai nst allogeneic NK-resistant Daudi cells and lung cancer cell lines: SBC-3, RERF-LC-AI and A549. IL-18 could augment IL-12-induced killer activity both at the optimal as well as suboptimal doses of the latter. However, IL-18 w as found to have little effect on the killer activity of MNC: induced by op timal or suboptimal dose of IL-2 or IL-15. Treatment of MNC with IL-18 in c ombination with IL-12 for a period of more than 4 days was observed to opti mally induce the killer activity. As for induction of IFN-gamma production by MNC, IL-18 augmented that induced by IL-2 and IL-15, as well as that ind uced by IL-12.. These results show the potential of IL-18 in combination wi th IL-12 for clinical application in treatment of cancer. (C) 2000 Internat ional Society for Immunopharmacology. Published by Elsevier Science Ltd. Al l rights reserved.