Tumor necrosis factor (TNF) is a multifunctional cytokine that plays a key role in regulating inflammation, immune functions, host defense, and apoptosis. TNF signals through two distinct cell surface receptors, TNFR1 (TNFRSF1A, CD120a) and TNFR2 (TNFRSF1B, CD120b). TNFR1, which contains a death domain (DD) within its intracytoplasmic region, is thought to be the key receptor for TNF signaling. This receptor can be released to the extracellular space by two mechanisms, ectodomain shedding and constitutive release of full-length 55-kDa TNFR1. Soluble TNFR1 could function as TNF-binding protein, inhibiting TNF bioactivity.