Immunomodulation of natural killer cell activity by flavone acetic acid: occurrence via induction of interferon alpha/beta.
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 alpha/beta type, while molecular hybridization studies demonstrated that FAA rapidly stimulated the production of IFN alpha mRNA in splenic leukocytes. In vivo administration of anti-IFN alpha/beta 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.
Laboratory of Experimental Immunology, National Cancer Institute, NCI-Frederick Cancer Research Facility, MD 21701-1013.
R L
RL
Hornung
H A
HA
Young
W J
WJ
Urba
R H
RH
Wiltrout
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D007370:Interferon Type I / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D013997:Time Factors
D000276:Adjuvants, Immunologic; D005419:Flavonoids; D007370:Interferon Type I; D012333:RNA, Messenger; C049328:flavone acetic acid