TLR4 and Sepsis: In CLP-treated septic mice, p38 MAPK inhibitor (SB203580) significantly inhibited high mobility group box 1 (HMGB-1) release and increased survival rate [41], HMGB-1 is an endogenous ligand for TLR4, in addition to LPS, and an important mediator of sepsis-associated death in experimental studies [42].