Indeed, a primary role of the TNF axis in the onset of sepsis hypothermia is well supported; the TNF receptor 1 (TNFR1) and matrix metalloproteinase 8 (MMP8, which cleaves pro-TNFα into its bioactive form) are required for typical hypothermia following acute lipopolysaccharide (LPS) endotoxemia or polymicrobial CLP in mice, whereas mice deficient in both TNFR1 and MMP8 did not exhibit hypothermia and were fully protected [40,41]. Here, MMP8 is linked to Sepsis.