In light of the important role of PKR in the regulation of Caspase-1-dependent pyroptosis11 and the receptor interacting protein (RIP)1/RIP3-dependent programmed necrosis (necroptosis)47, it will be important to determine whether P5 inhibits the LPS-induced HMGB1 release and/or sepsis-induced lung injury partly through impairing PKR-mediated pyroptosis and/or necroptosis. This evidence concerns the gene HMGB1 and Sepsis.