The in vitro development of cytotoxicity in response to granulocyte/macrophage-colony-stimulating factor or interferon gamma in the peripheral blood monocytes of patients with solid tumors: modulation by arachidonic acid metabolic inhibitors.
The capacity of granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interferon gamma (IFN gamma) to elicit monocyte cytotoxicity in vitro in the peripheral blood monocytes of patients with solid tumors was investigated. The cytotoxicity elicited by IFN gamma was significantly reduced in cancer patient monocytes compared to normal monocytes. The cytotoxicity elicited by GM-CSF, however, was comparable between cancer patient monocytes and normal monocytes, but was lower than that induced by IFN gamma. Indomethacin, a cyclooxygenase inhibitor, significantly augmented IFN gamma-elicited cytotoxicity in cancer patient monocytes, but not in normal monocytes. In contrast, indomethacin augmented GM-CSF-elicited cytotoxicity in both cancer patient monocytes and normal monocytes. Nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, was found to suppress cytotoxicity in response to IFN gamma and GM-CSF in both cancer patient monocytes and normal monocytes. The addition of leukotrienes to NDGA-treated cultures restored the development of cytotoxicity. Thus there are differences in the in vitro response of cancer patient monocytes and normal monocytes to distinct biological activators. Furthermore, these responses can be manipulated by agents that modulate arachidonic acid metabolism.
Braun
D P
DP
Section of Medical Oncology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
Siziopikou
K P
KP
Casey
L C
LC
Harris
J E
JE
D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D015289:Leukotrienes / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol / Q000494:pharmacology; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D010105:Oxygenases / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001095:Arachidonic Acids; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D009637:Masoprocol; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010105:Oxygenases; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin