INTERLEUKIN (IL)-6 AS A PANCREAS CARCINOMA-DERIVED VASCULAR-PERMEABILITY REGULATOR IN-VITRO

The interaction between pancreas adenocarcinoma and vascular endotheli al cells in vitro was investigated. Culture media of pancreas carcinom a cells PCI-10, but not PCI-24, induced an augmented albumin permeabil ity across the endothelial monolayer, an event which was blocked by th e calmodulin antagonist, W-7. Only marginal inhibitory effects were ob tained using protein kinase inhibitors, H-7 and HA-1004. When cytokine production by pancreas carcinoma cells was examined, production of IL -6 in large amounts by PCI-10, but not by PCI-24 cells was evident. As recombinant IL-6 generated a dose-dependent permeability increase, an d as this effect was inhibited by W-7, we considered that the enhancem ent of vascular permeability was mediated by this cytokine. The activi ty of culture supernatants for enhanced permeability was almost comple tely absorbed by the addition of an antibody specific for IL-6. Tumor- derived IL-6 as a soluble mediator regulates vascular permeability in vitro, and the production of this factor by pancreas adenocarcinoma ce lls presumably modulates biologic behavior.