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Inhibition of the Activation of Nuclear Factor-κB as a Novel Therapeutic Approach for SIRS and Septic Shock

  • G. Wray
  • C. Thiemermann
Conference paper
  • 124 Downloads
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 1998)

Abstract

It is now widely accepted that the release of pro-inflammatory cytokines [e.g., tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6], the expression on endothelium and neutrophils of adhesion molecules, and the overproduction of vasoactive mediators (e.g., nitric oxide, eicosanoids) play important roles in the pathophysiology of sepsis and septic shock. The expression of inducible genes leading to the formation of these proteins and autacoids relies on transcription factors which are either controlled by (other) inducible genes and, hence, require de novo protein synthesis or alternatively by so-called “primary transcription factors”. Among the latter, nuclear factor-kappa B (NF-κB) has received a considerable amount of attention because of its unique mechanism of activation, its active role in cytoplasmic/nuclear signaling, and its rapid response to pathogenic stimulation of cells [1,2]. NF-κB was first identified some 10 years ago as a regulator of the expression of the kappa-light chain gene in murine B lymphocytes, but has subsequently been identified in most, if not all cell types studied [3–5]. In the last few years, it has become apparent that NF-κB plays a central role in the regulation of many genes responsible for the generation of proteins and mediators which play a role in local and systemic inflammation as well as circulatory shock. This article reviews the mechanisms involved in the regulation of the activation of NF-κB, highlights the consequences of the activation of this transcription factor and points to novel therapeutic approaches aimed at preventing the activation of NF-κB in animal models of endotoxin shock.

Keywords

Septic Shock Mean Arterial Pressure Systemic Inflammatory Response Syndrome Multiple Organ Dysfunction Syndrome Pancreatic Injury 
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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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • G. Wray
  • C. Thiemermann

There are no affiliations available

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