Genetic ablation of RIPK1 and RIPK3 or treatment with Nec-1 provided significant protection against TNF-induced lethal SIRS and diminished circulating DAMPs level, suggesting the importance of both RIPK1 and RIPK3 in mediating cellular damage and mortality by necroptosis during TNF-induced SIRS [46]. This evidence concerns the gene PCSK1 and systemic inflammatory response syndrome.