title: Decreased pro-inflammatory cytokine production by LPS-stimulated PBMC upon in vitro incubation with the flavonoids apigenin, luteolin or chrysin, due to selective elimination of monocytes/macrophages.
abstract: Apigenin and its structural analogues chrysin and luteolin were used to evaluate their capacity to inhibit the production of pro-inflammatory cytokines by lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMC). Furthermore, flowcytometric analysis was performed to compare the effects of apigenin, chrysin, luteolin, quercetin and naringenin on the different cell types present in PBMC. LPS-stimulated PBMC were cultured in the presence of the flavonoids and TNFalpha, IL-1beta and IL-6 were measured in the supernatants. In parallel, metabolic activity of the PBMC was determined by measuring succinate dehydrogenase activity. Apigenin, chrysin and luteolin dose-dependently inhibited both pro-inflammatory cytokine production and metabolic activity of LPS-stimulated PBMC. With increasing concentration of apigenin, chrysin or luteolin the monocytes/macrophages disappeared as measured by flowcytometry. This also appeared to occur in the non-LPS-stimulated PBMC. At the same time there was an increase in dead cells. T- and B-lymphocytes were not affected. Quercetin and naringenin had virtually no effects on cytokines, metabolic activity or on the number of cells in the studied cell populations. In conclusion, monocytes were specifically eliminated in PBMC by apigenin, chrysin or luteolin treatment in vitro at low concentrations (around 8 microM), in which apigenin appeared to be the most potent.
authors.affiliation: Numico-Research, P.O. Box 7005, Wageningen 6700, The Netherlands. sander.hougee@numico-research.nl
authors.forename: Sander
authors.initials: S
authors.lastname: Hougee
authors.forename: Annemarie
authors.initials: A
authors.lastname: Sanders
authors.forename: Joyce
authors.initials: J
authors.lastname: Faber
authors.forename: Yvo M F
authors.initials: YM
authors.lastname: Graus
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.forename: H Friso
authors.initials: HF
authors.lastname: Smit
authors.forename: Maarten A
authors.initials: MA
authors.lastname: Hoijer
mesh_terms: D000328:Adult; D047310:Apigenin / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D047311:Luteolin / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged
chemical_list: D016207:Cytokines; D005419:Flavonoids; D008070:Lipopolysaccharides; C043561:chrysin; D047310:Apigenin; D047311:Luteolin