HMGB1 in the immunology of sepsis (not septic shock) and arthritis.

TLDR: Evidence implicating high mobility group box 1 (HMGB1) as an immunological mediator of severe sepsis is discussed and renewed interest in a molecule first described as an abundant nuclear and cytosolic DNA-binding protein is renewed.

Abstract: Publisher Summary This chapter discusses evidence implicating high mobility group box 1 (HMGB1) as an immunological mediator of severe sepsis An important contrast is made to distinguish the immunology of sepsis as distinct from the immunology of septic shock, a syndrome mediated by tumor necrosis factor (TNF) HMGB1 is produced during severe sepsis in humans and animals, and passive immunization with neutralizing anti-HMGB1 antibodies prevents lethality from established sepsis in animals HMGB1 administration does not cause shock, but it is lethal, in part by causing epithelial cell barrier dysfunction It is a proinflammatory mediator that contributes to the development of arthritis in animals and is produced in humans with rheumatoid arthritis; monoclonal anti-HMGB1 antibodies are in preclinical development for this therapeutic target The identification of these immunological and cytokine activities of HMGB1 has renewed interest in a molecule first described as an abundant nuclear and cytosolic DNA-binding protein There is only one Food and Drug Administration (FDA) approved treatment for sepsis, activated protein C, a partially effective anti-inflammatory and anti-coagulant therapy approved for use in a subset of patients with severe sepsis