TLR4 and Sepsis: 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