RIPK3-mediated necroptosis can initiate a ‘cell death storm’ in sepsis with the release of DAMPs, such as high-mobility group box 1 (HMGB1), IL-1α, DNA fragments, mitochondrial content, uric acid, ATP, heat shock proteins and cold-inducible RNA-binding protein (CIRP) to provoke a strong inflammatory response [24,26,27]. Here, HMGB1 is linked to Sepsis.