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Related Experiment Videos

Endotoxin tolerance: a review.

Michael A West1, Wyrta Heagy

  • 1Northwestern University, Department of Surgery, Chicago, IL 60611, USA. mwest@northwestern.edu

Critical Care Medicine
|January 10, 2002
PubMed
Summary
This summary is machine-generated.

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Endotoxin tolerance describes how prior exposure to bacterial endotoxin alters immune cell responses. This phenomenon, observed in both animals and humans, involves significant changes in inflammatory mediator production.

Area of Science:

  • Immunology
  • Microbiology
  • Cellular Biology

Background:

  • Endotoxin tolerance, initially observed in animal models, involves altered immune responses to bacterial endotoxins.
  • Two phases exist: early (cellular activation) and late (antibody development).
  • Recent research focuses on the mechanisms behind this altered responsiveness.

Purpose of the Study:

  • To investigate the mechanisms of endotoxin tolerance in host immune cells.
  • To characterize the 'lipopolysaccharide-tolerant' phenotype in macrophages and monocytes.
  • To explore the relevance of endotoxin tolerance in human inflammatory conditions.

Main Methods:

  • Exposing host immune cells (macrophages, monocytes) to endotoxin for 3-24 hours.
  • Analyzing cellular responses upon rechallenge with endotoxin or lipopolysaccharide.

Related Experiment Videos

  • Observing changes in cytokine production, enzyme activation, and signaling pathways.

    • Main Results:

    • Tolerant immune cells exhibit inhibited lipopolysaccharide-stimulated tumor necrosis factor production.
    • Altered release of interleukin-1 and interleukin-6 was observed.
    • Enhanced cyclooxygenase-2 activation, inhibited mitogen-activated protein kinase activation, and impaired nuclear factor-kappa B translocation characterize the tolerant phenotype.
    • Human monocytes and macrophages can achieve tolerance, mirroring characteristics seen in sepsis patients.

    Conclusions:

    • Endotoxin tolerance is a significant immunological phenomenon involving profound alterations in immune cell function.
    • The characterized 'lipopolysaccharide-tolerant' phenotype provides insights into immune dysregulation.
    • Endotoxin tolerance mechanisms in monocytes are relevant to human diseases like sepsis and systemic inflammatory response syndrome.