Tumor necrosis factor (TNF, tumor necrosis factor alpha, TNFα, cachexin, or cachectin) is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction Iplays a central role in inflammation, immune system development, apoptosis, and lipid metabolism. It is produced by a wide variety of immune, epithelial, endothelial, and tumor cells. Shedding of membrane bound TNF-alpha by TACE (ADAM17) releases the bioactive cytokine. TNF-alpha binds TNF RI and TNF RII and induces apoptotic signaling through the death domain of TNF RI.