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Mechanisms of Sepsis-Induced Organ Dysfunction and Recovery pp 67–75Cite as

The Significance of HMGB1, a Late-Acting Pro-inflammatory Cytokine

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Part of the Update in Intensive Care and Emergency Medicine book series (UICMSOFT,volume 44)

Conclusion

HMGB1 is a novel late mediator of inflammatory responses that contributes to ALI and lethal sepsis. It appears to interact with at least three receptors, including RAGE, TLR2, and TLR4, potentially explaining the similarities in cellular activation induced by HMGB1 and bacterial products, such as LPS or peptidoglycan. However, the multiple receptors involved in HMGB1 signaling also provide insights into the differences in gene expression produced by cellular interaction with this mediator. Unlike the situation with classically described pro-inflammatory cytokines, such as TNF-α or IL-1β, where blockade is only effective in improving outcome from experimental sepsis if administered before or very early in the course of sepsis, inhibition of HMGB1 with specific antibodies or the HMGB1 A box sequence still reduces mortality even if performed up to 24 hours after the initiation of the septic insult. Such findings suggest that HMGB1 may be an appropriate therapeutic target in patients with sepsis or ALI, since it may participate in the pathogenesis of organ dysfunction and mortality even at later time points when such patients present for hospital or ICU admission.

Keywords

  • Acute Lung Injury
  • Ethyl Pyruvate
  • Late Mediator
  • Postinjury Multiple Organ Failure

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Authors and Affiliations

  1. Department of Medicine, University of Alabama, 1530 3rd Ave S, Birmingham, AL, 35294-0012, USA

    E. Abraham

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  1. E. Abraham
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Editors and Affiliations

  1. Health Sciences Center, Division Pulmonary & Critical Care Medicine, University of Colorado, E. Ninth Avenue 4200, 80262, Denver, CO, USA

    Edward Abraham MD

  2. Bloomsbury Institute of Intensive Care, Division Medicine, University College Hospital, Gower Street, WC1E 6BT, London, UK

    Mervyn Singer MD

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Abraham, E. (2007). The Significance of HMGB1, a Late-Acting Pro-inflammatory Cytokine. In: Abraham, E., Singer, M. (eds) Mechanisms of Sepsis-Induced Organ Dysfunction and Recovery. Update in Intensive Care and Emergency Medicine, vol 44. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-30328-6_5

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  • DOI: https://doi.org/10.1007/3-540-30328-6_5

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-30157-8

  • Online ISBN: 978-3-540-30328-2

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