Endotoxin tolerance: new mechanisms, molecules and clinical significance.

Trends Immunol 2009 Oct 24;30(10):475-87. Epub 2009 Sep 24.

Singapore Immunology Network, Biomedical Sciences Institutes, Agency for Science, Technology and Research, #04-01 Immunos, 8A Biomedical Drive, 138648 Singapore.

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.

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http://dx.doi.org/10.1016/j.it.2009.07.009DOI Listing
October 2009
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