INCREASED RELEASE OF INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR BY INTERLEUKIN-2-INDUCED LYMPHOKINE-ACTIVATED KILLER-CELLS IN THE PRESENCE OF CISPLATIN AND FK-565

The supernatants of peripheral blood lymphocytes cultured in interleukin-2 (IL-2) for 4 days contained tumour necrosis factor (TNF) and interleukin-1 (IL-1). Addition of cisplatin (CP) or FK-565 to these cultures increased the level of both of these cytokines in culture supernatants. Furthermore, when the LAK cells induced by culture with IL-2 in the presence or absence of CP/FK-565 were co-cultured with tumour cells, the production of these cytokines was significantly enhanced. The level of enhancement depended on the ratio of LAK cells to tumour cells used and the length of coincubation of the two cell types. Culture supernatants of LAK cells and LAK cells stimulated by tumour cells were also cytotoxic to MCF-7 and U937 cells in 72 h cytotoxic assay, and antibodies specific for TNF and IL-1 inhibited the supernatant-mediated cytotoxicity. These results suggest that, in addition to the up-regulation of IL-2-induced LAK activity, treatment of PBL with CP/FK-565 leads to enhanced production of various cytokines with potential antitumour and immunoregulatory activity.