The flavonoid, quercetin, differentially regulates Th-1 (IFNγ) and Th-2 (IL4) cytokine gene expression by normal peripheral blood mononuclear cells

Abstract

Flavonoids are plant metabolites that are dietary antioxidants and exert significant anti-tumor, anti-allergic, anti-inflammatory and anti-viral effects. It is generally accepted that Th-1 derived cytokines such as IL-2, IFNgamma and IL-12 promote cellular immunity while Th-2 derived cytokines such as IL-4, IL-5, IL-6 exert negative immunoregulatory effects on cellular immunity while upregulating humoral immunity. The molecular mechanisms underlying the biological activities of flavonoids have not been elucidated. We hypothesize that the flavonoid, quercetin, exert significant anti-viral and anti-tumor effects possibly by modulating the production of Th-1 and Th-2 derived cytokines. Peripheral blood mononuclear cells (PBMC, 1 x 10(6) cells/ml) from normal subjects were cultured with different concentrations of quercetin (0.5-50 microM) for 24-72 h and supernates were quantitated for IFN-gamma and IL-4 by ELISA and antiviral activity of IFNgamma by bioassay. FACS analysis was done to determine the number of IFN-gamma and IL-4 positive cells and RT-PCR was done to quantitate gene expression. Quercetin significantly induces the gene expression as well as the production of Th-1 derived IFNgamma and the downregulates Th-2 derived IL-4 by normal PBMC. Further, quercetin treatment increased the phenotypic expression of IFNgamma cells and decreased IL-4 positive cells by FACS analysis, which corroborate with protein secretion and gene expression studies. These results suggest that the beneficial immuno-stimulatory effects of quercetin may be mediated through the induction of Th-1 derived cytokine, IFNgamma, and inhibition of Th-2 derived cytokine, IL-4.

Naringin dietary supplementation at 0.15% rates does not provide protection against sub-clinical acidosis and does not affect the responses of fattening lambs to road transportation

“…The lacking differences in cytokine IFN-g production are in agreement with those described by Jacob et al (2008) in humans for a combination of lycopene and vitamin C. On the contrary, quercetin added to cell cultures showed a dose-dependent upregulation of gene expression; thus, increasing IFN-g production (Nair et al, 2002). All these divergent results might be due once again to different doses of flavonoids used in these studies.…”

Inhibition of T-cell-Dependent Antibody Production by Quercetin in Mice

“…The same compound also inhibits the cytotoxic effect of cytotoxic T-cells (Schuwartz et al, 1982). Recently, quercetin was also demonstrated to enhance interferon (IFN)-γ production, but inhibited interleukin (IL)-4 production, suggesting a suppressive action of humoral immunity (Nair et al, 2002). However, no report has been available to describe the in vivo effects of quercetin on antibody production, and to our knowledge this is the first report showing the inhibitory activity of quercetin on antibody production in vivo.…”

The effects of dietary Eleutherine bulbosa on the growth, leukocyte profile, and digestive enzyme activity of the striped catfish Pangasianodon hypophthalmus

“…Though the underlying mechanism(s) whereby EAE boosts the haematological indices of P. hypophthalmus is not properly understood, nevertheless, Nair et al (2002) and Lyu and Park (2005) have suggested that flavonoid plant metabolites in the bulbs of E. americana (Kuntorini et al 2016) may contribute to promoting cellular immunity by modulating Th-1 derived cytokines such as IL-2 (Interleukin 2) and INFγ (Interferon). Flavonoids found in the EAE may be biocatalysts in the production of leukocytes and in stimulating nonspecific cellular immunity by leukocytes.…”