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Related Experiment Videos

Cytokine down-regulation in endotoxin tolerance

M Mengozzi1, P Ghezzi

  • 1Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

European Cytokine Network
|March 1, 1993
PubMed
Summary

Lipopolysaccharide (LPS) tolerance down-regulates cytokine production in various species and humans. This immune desensitization is specific, reversible, and involves complex in vivo mechanisms beyond simple cell desensitization.

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Lipopolysaccharide (LPS) tolerance is a phenomenon where cells become less responsive to subsequent LPS stimulation.
  • This tolerance is characterized by the down-regulation of cytokine production, a key immune response.
  • LPS tolerance has been observed across diverse species and cell types, both in vivo and in vitro.

Purpose of the Study:

  • To investigate the characteristics of LPS tolerance.
  • To determine the specificity and reversibility of LPS-induced immune desensitization.
  • To explore the contributing factors to LPS tolerance in vivo.

Main Methods:

  • Induction of LPS tolerance in vitro and in vivo.
  • Assessment of cytokine production following LPS stimulation.
  • Testing reversibility of tolerance using co-administration of LPS with IFN-gamma or PMA.
  • Evaluating cytokine response to non-LPS stimuli to assess specificity.

Main Results:

  • Cytokine production is significantly down-regulated in LPS tolerance.
  • LPS tolerance can be induced in various species and cell types, in vivo and in vitro.
  • The refractory state is reversible and can be bypassed by specific co-treatments.
  • Tolerance is specific, with cytokine production still inducible by non-LPS stimuli, indicating true LPS desensitization.
  • In vivo LPS tolerance involves complex mechanisms including non-specific blockade, hormonal feedback, and altered macrophage activity.

Conclusions:

  • LPS tolerance represents a specific desensitization of cytokine-producing cells.
  • Reversibility and specificity of LPS tolerance are demonstrated.
  • In vivo LPS tolerance is a multifactorial process extending beyond simple cellular desensitization.

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