The pro-inflammatory type of HMGB1 was predominantly detected at weeks 4–8 in sepsis survivors.194 Studies have claimed that pro-inflammatory effect largely depend on the B box due to its much lower dissociation rate with TLR4.198 Besides, disulfide form of HMGB1 alone could prime NLRP3 inflammasome activation for stimulating excessive cytokine production.199. This evidence concerns the gene NLRP3 and Sepsis.