Resveratrol, a natural stilbene in grapes and wine, enhances intraphagocytosis in human promonocytes: A co-factor in antiinflammatory and anticancer chemopreventive activity

Trans-resveratrol, a natural stilbene present in wine and grapes, has been studied mainly for its anti-inflammatory and anticancer activities. In this study the activity of resveratrol on proliferative immunological parameter s (differentiation, apoptosis, phagocytosis and intracellular killing) was studied using a U937 human promonocytic cell line in comparison with anothe r polyphenol, quercetin. After incubation of the pathogen, Candida albicans , intracellular killing by macrophage-like cells was decreased by quercetin and resveratrol 10 mu M but was enhanced by resveratrol 1 mu M after 20 h of treatment. Phagocytosis rate, expressed as phagocytosis frequency: (i.e. , percentage number of phagocytosing cells/total cells) at 20 h was highest with resveratrol 10 mu M and was higher with quercetin 10 mu M than with r esveratrol 1 mu M. The phagocytosis index exhibited the same trend. While b oth polyphenols demonstrated cytostatic activity on U937 growth, a prointra phagocytic effect for resveratrol 10 mu M-treated cells at 10 min, resverat rol 1 mu M-treated cells at 20 h and resveratrol 10 CIM-treated cells at 48 h was observed. Morphological examination with optic microscopy demonstrat ed both apoptotic and differentiating cells, even after 10 min treatment. R esveratrol-induced apoptosis (following 4 h treatment) was confirmed by flo w cytometry at concentrations as low as 1 mu M and 100 nM in the assay for detection of membrane phosphatidylserine. Resveratrol- or quercetin-treated , but unstimulated cells, did not produce tumor necrosis factor-alpha prote in. As phosphatidylserine externalization triggers specific recognition by monocytes and macrophages, removal of intact apoptotic cells is important a ) in cell population selection and differentiation for antiblastic therapy and b) in preventing the release of toxic inflammatory substances such as r eactive oxygen substances and proteolytic enzymes by dying cells. This obse rvation suggests that wine polyphenols, at the same concentrations as those found in plasma after moderate wine consumption, are important cofactors i n antiinfective, antiinflammatory and anticancer nonspecific immune reactio ns.