Immunomodulation of Natural Killer Cell Activity by Flavone Acetic Acid: Occurrence Via Induction of Interferon /beta

Abstract
The investigational drug flavone acetic acid (FAA) systemically augments natural killer (NK) cell activity in normal and tumor-bearing mice and in human cancer patients. The results from the present investigation demonstrate that in vivo administration of FAA induces in a dose-dependent manner high levels of serum interferon (IFN) within 4 hours in BALB/c, C57BL/6, and BALB/c nude mice. Antibody neutralization studies indicated that FAA induced IFN of the α/β type, while molecular hybridization studies demonstrated that FAA rapidly stimulated the production of IFN a mRNA in splenic leukocytes. In vivo administration of anti-IFN α/β antibodies to FAA-treated mice inhibited the FAA-induced augmentation of splenic NK cell activity at 4 hours. These results suggest that FAA mediates its anti-tumor effects indirectly by immunomodulation as well as directly by antiproliferative or cytotoxic activity. [J Natl Cancer Inst 1988;80:1226–1231]

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