HMGB1 and Sepsis: TLR4 is a signal transduction receptor for bacterial LPS, and TLR4 inhibition is considered to be critical for two reasons: firstly, circulating LPS levels increase in sepsis, even in infections caused by Gram-positive cocci; secondly, some of the endogenous molecules released by the host cell during sepsis are TLR4 sensitizers, such as heat shock protein 60, HMGB-1, and hyaluronic acid.