Several DAMPs have been identified, including heat shock proteins, S100 proteins, hyaluronan, heparin sulfate, RNA, DNA, and high-mobility group box 1 (HMGB1).1 Endogenous DAMPs are elevated and contribute to poor outcomes in several inflammatory models, both infectious and noninfectious, including sepsis,2 acute lung injury,3 pancreatitis,4 burns,5 and trauma.6, 7 These molecules are recognized by PRRs on various cell types, and in turn, drive the inflammatory response. Here, HMGB1 is linked to injury.