Lymphocyte responses to the polyphenol, oenothein B, and the influence of age on these responses

Abstract

Innate lymphocytes, such as NK cells, play an important role in a number of human diseases. Therefore, they have become popular target cells for new therapeutics. Studies to identify materials that stimulate these cells have identified a number of molecules from nutritional supplements which can activate and/or inhibit their activity. While the use of nutritional supplements has potential to enhance the activity of innate lymphocytes to help treat and prevent disease, there is still much which is currently unknown about the activity of these compounds. Previous work has identified oenothein B, an ellagitannin isolated from Epilobium angustifolium, to be a stimulant for myeloid cells. In this study, we further examined the immunomodulatory effects of oenothein B and identified that it also stimulates lymphocytes. We found that oenothein B induces the production of IFN gamma by NK cells and both alpha beta and gamma delta T cells. In addition to inducing the production of IFN gamma by NK cells alone, oenothein B also enhances IFN gamma production in response to secondary stimuli, such as IL-18 or a tumor cell line, in a synergistic manner. We also identified a novel effect of aging on the lymphocyte response to oenothein B. The induction of IFN gamma, as well as GM-CSF, production by T cells in response to oenothein B increases in adults compared to young individuals. The predominant producers of IFN gamma in response to oenothein B also shift from the NK cell population in young individuals to the T cell population in adults. The increase in cytokine production in adult T cells correlates with increasing numbers of CD45RO+ T cells, which produce more cytokines in response to oenothein B than CD45RO- T cells. This influence of aging on the immune response to oenothein B may be applicable to numerous nutritional supplements which stimulate innate immunity and could be an important variable in the effectiveness of these compounds in improving human health. In this dissertation, we identify age as an important factor which should be taken into account when examining the effect of polyphenols on innate immunity and could have important implications for optimizing the benefit of immunomodulatory polyphenols.