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.