HMGB1 and Sepsis: RAGE interacts with various DAMPs, such as high mobility group box 1 (HMBG1), S100A8/9, and MAC-1 (a heterodimer of CD11b and CD18), in addition to advanced glycosylation end products (AGEs).10Elevated levels of AGEs have been observed in the heart and brain of sepsis patients, potentially initiating inflammation in these areas.11Recent preclinical studies have highlighted the possible benefits of inhibiting the interaction between RAGE and a key molecule in its signaling pathway.11In sepsis, TREM-1 is abundantly expressed on monocytes and neutrophils.