Inhibitory effects of cytokines on vascular endothelial cells: synergistic interactions among interferon-gamma, tumor necrosis factor-alpha, and interleukin-1.
The formation of new blood vessels is critical to tumor growth and metastasis and since endothelial cells are the principal cell type comprising such blood vessels, we carried out experiments to test whether the growth of endothelial cells in vitro can be inhibited by low doses of combinations of cytokines. We show that growth of mouse aortic endothelial cells can be inhibited in vitro by combinations of cytokines that, administered singly even at ten times higher concentrations, have only marginal effects. In particular, interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma), acting synergistically at low, subthreshold concentrations, are able to completely inhibit the growth of endothelial cells in vitro.
Norioka
K
K
Center for Developmental Biology, University of Wisconsin, Madison 53706.
Borden
E C
EC
Auerbach
R
R
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma