The effects of flavonoids on the immune system are complex and poorly understood. Depending on the conditions, flavonoids may inhibit, assist, or have no effect on immune function. Their effects on immune function are due to their ability to inhibit eicosanoid-mediated inflammation, histamine-induced inflammation, PTK or PKC activity, cell motility, or several of these.
Many flavonoids can impede leukocyte proliferation and function in vitro. For example, genistein can inhibit T-cell and NK-cell activity in vitro at IC50 concentrations similar to that of cancer cell inhibition (about 1 to 100 mM).98-102 This effect appears to be due partly to inhibition of PTK activity. Similarly, studies have reported that apigenin and quercetin can lower the generation and function of CD8 cytotoxic T cells in vitro (at about 5 to 20 mM).103,104,105
The above-cited studies tested pure flavonoids in vitro; flavonoids are present as glucuronide conjugates in vivo, however, and the conjugate forms appear to be much less inhibitory than the pure forms. For example, glu-curonide conjugates of genistein inhibited NK cell activity at about 50-fold higher concentrations than that of free genistein.99 In fact, genistein conjugates enhanced NK cell activity at concentrations that are relevant for therapy (0.1 to 10 mM). Moreover, quercetin enhanced natural killer cell activity in rats at oral doses relevant for therapy (at about 1.6 grams per day, as scaled to hu mans).106 Similarly, oral administration of quercetin (at about 380 milligrams per day, as scaled to humans) increased macrophage-mediated antiviral effects in mice. Lastly, even in-vitro studies have reported that at low concentrations flavonoids can act as immunostimu-lants.
Clearly, additional work remains to understand the effects of flavonoids on immune function and to determine how these effects may influence tumor progression. It does seem, however, that at doses relevant to humans, immunostimulation or no effect on the immune system is more likely to occur than an immunosuppressive effect.
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