TNF and inflammatory bowel disease: In an attempt to dissect the mechanisms that suppress Sirt1 in IBD, we showed that stimulation of control intestinal mucosal cells with tumor necrosis factor (TNF)-α and interleukin (IL)-21 reduced Sirt1 expression while blockade of the activity of these two cytokines upregulated Sirt1 in IBD lamina propria mononuclear cells (LPMC) (10).