Therapeutic potential of HMGB1-targeting agents in sepsis.
Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. The inflammatory response is partly mediated by innate immune cells (such as macrophages, monocytes and neutrophils), which not only ingest and eliminate invading pathogens but also initiate an inflammatory response upon recognition of pathogen-associated molecular patterns (PAMPs). The prevailing theories of sepsis as a dysregulated inflammatory response, as manifested by excessive release of inflammatory mediators such as tumour necrosis factor and high-mobility group box 1 protein (HMGB1), are supported by extensive studies employing animal models of sepsis. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of experimental sepsis, and discuss the therapeutic potential of several HMGB1-targeting agents (including neutralising antibodies and steroid-like tanshinones) in experimental sepsis.
Wang
Haichao
H
Laboratory of Emergency Medicine, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA. hwang@nshs.edu
Zhu
Shu
S
Zhou
Rongrong
R
Li
Wei
W
Sama
Andrew E
AE
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000502:physiology; D007113:Immunity, Innate / Q000502:physiology; D051379:Mice; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D015398:Signal Transduction
D000890:Anti-Infective Agents; D024243:HMGB1 Protein