Recent studies have clarified the mechanism of development and progression in sepsis [1]. However, the sepsis remains a serious problem in critically ill patients. The mortality in patients with sepsis is caused by bacterial endotoxin. Endotoxin stimulates macrophages/monocytes to release high mobility group box 1 (HMGB1), a chromatin protein with a cytokine function. The extracellular HMGB1 acts as a pro-inflammatory cytokine following releases from necrotic cells or macrophages activated by tumor necrosis factor (TNF)-α or interferon (IFN)-γ through the toll-like receptor -2 or -4 and receptor for advanced glycation end-products (RAGE), suggesting “cytokine loops” in inflammatory disease such as rheumatoid arthritis (RA) and atherosclerosis [2,3].
