Suppression of IL‐2 Production and Proliferation of CD4+ T Cells by Tuberostemonine O

Tuberostemonine stereoisomers are natural alkaloids found in Stemona tuberosa, that are known to have anti‐inflammatory and anti‐infective properties. Tuberostemonine alkaloids inhibit inflammation by suppressing the expression of inflammatory mediators such as cyclooxygenase and nitric oxide synthase. However, the direct immunomodulatory properties of tuberostemonine alkaloids in T cells have not been elucidated so far. In this study, the activities in T cells of tuberostemonine N (TbN) and a novel alkaloid, tuberostemonine O (TbO), isolated from S. tuberosa, were investigated. Although TbN did not have a significant effect on cytokine production in splenic T cells, TbO selectively suppressed interleukin (IL)‐2 production. Moreover, TbO, but not TbN, significantly inhibited IL‐2 production by primary CD4⁺ T cells and delayed the T‐cell proliferation in a dose‐dependent manner. Addition of excess recombinant IL‐2 restored the decreased cell‐division rates in TbO‐treated CD4⁺ T cells to control levels. Collectively, these findings suggest that the immunomodulatory effects of TbO occurred by the suppression of IL‐2 expression and IL‐2‐induced T‐cell proliferation, suggesting a potential beneficial role of tuberostemonine alkaloids for the control of chronic inflammatory and autoimmune diseases caused by hyperactivated T cells.