TNF and Sepsis: In sepsis, extracellular histones can act as damage-associated-molecular-patterns (DAMPs), reacting with different receptors, including Toll-like receptor (TLR) 2, TLR4, or TLR9 [5], and triggering activation of multiple pro-inflammatory pathways, including myeloid differentiation primary response 88 (MyD88), which can induce release of interleukin (IL)-6 and tumor necrosis factor (TNF) alpha, nuclear factor-κB (NF-κB), and activate NLRP3 inflammasome-dependent pathways [8].