TNF and systemic inflammatory response syndrome: As described in section 6, RIPK1- and RIPK-3-mediated necroptosis drives increasedmortality during TNF-induced SIRS an effect that could be blocked by the presence ofcaspase-8, which promoted RIPK1 and/or RIPK3 cleavage and inhibitednecroptosis.53 Considering this fact,using caspases pan inhibitors like zVAD.fmk and VX-166 or specific inhibition ofcaspase-8 may trigger necroptosis, which may further deteriorate sepsis.