Endotoxin tolerance: new mechanisms, molecules and clinical significance

Trends Immunol. 2009 Oct;30(10):475-87. doi: 10.1016/j.it.2009.07.009. Epub 2009 Sep 24.


Prior exposure of innate immune cells like monocytes/macrophages to minute amounts of endotoxin cause them to become refractory to subsequent endotoxin challenge, a phenomenon called "endotoxin tolerance". Clinically, this state is associated with monocytes/macrophages in sepsis patients where they contribute to "immunosuppression" and mortality. The molecular mechanisms underlying endotoxin tolerance remain elusive. The recent appreciation of inflammation as a self-regulating process, the relative contribution of MyD88 versus TRIF signaling pathways in inducing activation or tolerance, plasticity of NF-kappaB function and the role of chromatin modification and microRNAs in LPS-induced gene reprogramming urges a re-evaluation of endotoxin tolerance. This review integrates these new findings into an up-to-date account of endotoxin tolerance, its molecular basis and clinical implications in different pathologies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Chromatin / metabolism
  • Endotoxins / immunology*
  • Humans
  • Immune Tolerance*
  • Lymphocytes / physiology
  • Macrophages / physiology
  • MicroRNAs / metabolism
  • Monocytes / physiology
  • Receptors, Chemokine / metabolism
  • Signal Transduction*
  • Systemic Inflammatory Response Syndrome / immunology
  • Toll-Like Receptors / metabolism


  • Chromatin
  • Endotoxins
  • MicroRNAs
  • Receptors, Chemokine
  • Toll-Like Receptors