Legionella pneumophilaReplication in Macrophages Inhibited by Selective Immunomodulatory Effects on Cytokine Formation by Epigallocatechin Gallate, a Major Form of Tea Catechins

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Abstract
Epigallocatechin gallate (EGCg) is a major form of tea catechin and has a variety of biological activities, including antitumor as well as antimicrobial activity against some pathogens. Although the biological activities of EGCg have been extensively studied, its immunological effects are not well known. In the present study, the ability of EGCg to modulate macrophage immune functions in an in vitroLegionella pneumophilainfection model of macrophages was examined. The study showed that EGCg inhibited the growth ofL. pneumophilain macrophages at a concentration as low as 0.5 μg/ml without any direct antibacterial effect on the organisms. The EGCg selectively upregulated the production of interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) and downregulated IL-10 production of macrophages induced byL. pneumophilainfection in a dose-dependent manner, but did not alter IL-6 production even at a high dose. The upregulation of the levels of macrophage gamma interferon (IFN-γ) mRNA by EGCg was also demonstrated. Treatment of macrophage cultures with anti-TNF-α and anti-IFN-γ monoclonal antibodies markedly abolished the anti-L. pneumophilaactivity of macrophages induced by the EGCg treatment. These results indicate that EGCg selectively alters the immune responses of macrophages toL. pneumophilaand leads to an enhanced anti-L. pneumophilaactivity of macrophages mediated by enhanced production of both TNF-α and IFN-γ. However, the enhancement of in vitro anti-L. pneumophilaactivity by EGCg may not be directly mediated by IL-10 and IL-12 production modulation. Thus, the results of this study revealed the immunomodulatory effect of EGCg on macrophages, which have a critical role in infections.