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Published on: April 11, 2012

Extracellular role of HMGB1 in inflammation and sepsis

H Wang1, H Yang, K J Tracey

  • 1Laboratory of Emergency Medicine, North Shore-LIJ Research Institute, Manhasset, NY 11030, USA. hwang@nshs.edu

Journal of Internal Medicine
|February 12, 2004
PubMed

Insights

High mobility group box 1 (HMGB1) acts as a cytokine mediator in lethal inflammation like sepsis and arthritis. Passive immunization with anti-HMGB1 antibodies protects against these conditions, highlighting HMGB1 as a therapeutic target.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • High mobility group box 1 (HMGB1) is a protein involved in various cellular functions.
  • HMGB1 has emerged as a key mediator of systemic and local inflammatory responses.
  • Its serum levels rise during endotoxemia, sepsis, and arthritis, with delayed kinetics compared to TNF and IL-1beta.

Purpose of the Study:

  • To elucidate the role of HMGB1 as a cytokine mediator in lethal systemic inflammation.
  • To investigate the therapeutic potential of targeting HMGB1 in inflammatory conditions.

Main Methods:

  • Analysis of HMGB1 serum levels in preclinical models of inflammation.
  • Investigating HMGB1's biological activities, including macrophage activation and endothelial cell effects.
  • Evaluating the protective effects of passive immunization with anti-HMGB1 antibodies.

Main Results:

  • HMGB1 mediates lethal systemic inflammation, arthritis, and acute lung injury.
  • HMGB1 activates macrophages to release proinflammatory cytokines.
  • Anti-HMGB1 antibodies provide significant protection against lethal endotoxemia, sepsis, and arthritis, even with delayed administration.

Conclusions:

  • HMGB1 is a critical cytokine mediator in severe inflammatory diseases.
  • Targeting HMGB1 activity and release presents a promising therapeutic strategy for inflammatory conditions.

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