Lymphokine-activated killer cytotoxicity against pancreas adenocarcinoma cell lines and vascular endothelial cells.

Eight pancreas carcinoma cell lines of duct cell origin (PCI-6, 10, 19, 24, 35, 43, 55, and 64) were established. Using one of these lines, PCI-24, human umbilical vein endothelial cells (HUVEC), and several recombinant cytokines, conditions and specificity of antl-PCI LAK induction were Investigated, with the focus on a search for lymphokine-activated killer (LAK) activity that differentiates neoplastic (PCI) from non-neoplastic (HUVEC) cells. Interferon-γ (IFN-γ), IFN-α, IL-4, 11–6, and IL-7, but not tumor necrosis factor-α (TNF-α) or IL-1β, induced a weak LAK activity against PCI-24, whereas IL-2-induced (1000U/mL) LAK exhibited a far more potent cytotoxicity. When these cytokines were added at the suboptimal dose IL-2 (100U/mL), no significant augmentation in LAK activity was induced. Staphylococcal protein A (SpA) induced LAK activity as potent as that seen with IL-2 (1000 U/mL). Both IL-2-induced and SpA-induced LAK had a potent, dose-dependent cytotoxicity against HUVEC. HUVEC inhibited both IL-2– and SpA-induced LAK cytotoxicity against PCI-24 to almost the same extent as seen with PCI-24. Thus, two potent LAK-inducers did not generate LAK activity that differentiates neoplastic from non-neoplastic cells. Thus, in vitro cytotoxicity of LAK agalnst non-neoplastic endothelial cells is unavoidable when handling cytokines in LAK induction.