Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils.
BACKGROUND
We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids and attempted to determine the fundamental structure of flavonoids related to inhibition. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody.


METHODS
Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days.


RESULTS
Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined.


CONCLUSIONS
Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases.
Hirano
Toru
T
Third Department of Internal Medicine, Osaka University Medical School, 2-2 Yamada-oka, Suita City, Osaka 565-0871, Japan.
Higa
Shinji
S
Arimitsu
Junsuke
J
Naka
Tetsuji
T
Shima
Yoshihito
Y
Ohshima
Shiro
S
Fujimoto
Minoru
M
Yamadori
Tomoki
T
Kawase
Ichiro
I
Tanaka
Toshio
T
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D047310:Apigenin; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D044948:Flavonols; D006801:Humans; D007073:Immunoglobulin E / Q000187:drug effects / Q000494:pharmacology; D018793:Interleukin-13 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D047311:Luteolin; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D018926:Anti-Allergic Agents; D000970:Antineoplastic Agents; D015415:Biomarkers; D005419:Flavonoids; D044948:Flavonols; D018793:Interleukin-13; D015847:Interleukin-4; D017997:Leukotriene C4; D007073:Immunoglobulin E; D047310:Apigenin; D047311:Luteolin; C017875:fisetin