TNF and Sepsis: In the early stage of sepsis, macrophages are excessively activated through the binding of toll-like receptor (TLR) with pathogen-associated molecular patterns (PAMPs) of the invading pathogen, such as lipopolysaccharide (LPS) in gram-negative bacteria, resulting in the excessive secretion of massive amounts of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)9, which is considered as one of the leading causes for the high mortality in the early stage of sepsis10,11.