HMGB1, a potent proinflammatory cytokine in sepsis.

High-mobility group box 1 (HMGB1), a highly conserved protein previously known as a DNA-binding protein involved in maintenance of nucleosome structure and regulation of gene transcription, was recently found to act as a potent proinflammatory cytokine during infection responses. Levels of HMGB1 increase in serum and tissues during infection, especially in sepsis. Sepsis, which is a systemic inflammatory response disease, is the most severe complication of infection and is a deadly disease, and HMGB1 acting as a potent proinflammatory cytokine involve in the delayed endotoxin lethality and systemic inflammatory response. A growing number of studies have demonstrated HMGB1 is a cytokine that can mediate inflammation and is a potential therapeutic target in experimental models of sepsis. To reduce sepsis-related mortality, a better understanding of HMGB1 is essential. In this article, we will describe the structure, release process, intracellular function, and cell surface receptors of HMGB1, but will primarily focus on its extracellular roles and mechanism in inflammation, especially in sepsis. Copyright 2010 Elsevier Ltd. All rights reserved.