TLR4 signaling is required for the expression of caspase-11, and genetic deletion of TLR4 almost blocked the expression of caspase-11; however, 8-ol treatment did not impact the expression of caspase-11 in LPS-treated macrophages and endotoxemia mice (Supplementary Figure S1), which indicated that 8-ol has no effect on TLR4 signaling and specifically inhibits the HMGB1-mediated caspase-11–dependent pathway. This evidence concerns the gene HMGB1 and serum lipopolysaccharide activity.