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Related Experiment Videos

Endotoxin tolerance: A review.

Michael A. West1, Wyrta Heagy

  • 1Northwestern University, Department of Surgery, Chicago, IL.

Critical Care Medicine
|March 14, 2002
PubMed
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Endotoxin tolerance, a state of reduced immune response, occurs when immune cells like macrophages are exposed to lipopolysaccharide. This tolerance impacts inflammatory cytokine production and signaling pathways.

Area of Science:

  • Immunology
  • Microbiology
  • Cellular Biology

Background:

  • Endotoxin tolerance was first observed as increased survival after lethal endotoxin doses following prior sublethal exposure.
  • Two phases exist: early (altered cellular activation) and late (antibody development).
  • Recent research shows renewed interest in the mechanisms behind altered endotoxin 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 diseases like sepsis.

Main Methods:

  • Exposing host immune cells (macrophages, monocytes) to endotoxin for 3-24 hours to induce tolerance.

Related Experiment Videos

  • Analyzing the "lipopolysaccharide-tolerant" phenotype by measuring cytokine production (TNF, IL-1, IL-6).
  • Assessing cellular signaling pathways including cyclooxygenase-2, mitogen-activated protein kinase, and nuclear factor-kappaB translocation.

    • Main Results:

    • Immune cells exposed to endotoxin become "tolerant," exhibiting altered responses upon rechallenge.
    • The tolerant phenotype includes inhibited lipopolysaccharide-stimulated tumor necrosis factor production.
    • Key alterations involve modified interleukin release, enhanced cyclooxygenase-2, inhibited mitogen-activated protein kinase activation, and impaired nuclear factor-kappaB translocation.

    Conclusions:

    • Macrophages and monocytes can be induced into a state of endotoxin tolerance.
    • Human monocytes from patients with systemic inflammatory response syndrome and sepsis display characteristics of endotoxin tolerance.
    • Understanding endotoxin tolerance mechanisms is crucial for managing inflammatory conditions and sepsis.