MLKL and systemic inflammatory response syndrome: It is widely accepted that necroptosis plays an essential role in systemic inflammatory response syndrome (SIRS).24,37 In line with the findings on the necroptosis-promoting role of HSPA8 inhibitor, pharmacological application of HSPA8 inhibitor synergistically increased SIRS-induced lethality in WT mice, but these effects were reduced in Rip3−/− and Mlkl−/− mice (Fig. 1g).