Figure 7.

A model of the mechanism whereby zVAD ameliorates endotoxin shock pathology. The schematic diagram indicates that mice treated with lipopolysaccharide (LPS) would undergo macrophage activation, leading to cytokine storm that would cause inflammation and injury in mice. However, mice pretreated with zVAD (i.p.) prior to LPS challenge would exhibit macrophage necroptosis and the accumulation of MDSCs. Both of the above effects can largely inhibit macrophage activation, thereby reducing cytokine production and avoiding severe damage. Thus, zVAD can alleviate LPS-induced endotoxic shock by inducing the necroptosis of macrophages and promoting MDSCs-mediated inhibition of macrophage activation.