Cited by 1,318Immune Response and InflammationImmune responses and vaccinationsSepsis Diagnosis and Treatment

Endotoxin tolerance: new mechanisms, molecules and clinical significance

Biswas, Subhra K., Lopez-Collazo, Eduardo·2009·Trends in Immunology

Abstract

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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Crossref · 10.1016/j.it.2009.07.009

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  • LPS-stimulated classically activated macrophages become TLR-tolerant and unable to produce similarly elevated pro-inflammatory cytokines upon second LPS exposure, but retain ability to produce anti-inflammatory cytokines like IL-10.

    “For example, in vitro experiments have shown that LPS stimulated, classically activated macrophages, become Toll-like receptor (TLR)-tolerant and unable to produce similarly elevated levels of pro-inflammatory cytokines upon second exposure to LPS [16–18].”

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Authors
Biswas, S. K., & Lopez-Collazo, E.
Affiliations
Agency for Science, Technology and Research (SG)
Corresponding author
Biswas, Subhra K.
Venue
Trends in Immunology
Publisher
Elsevier BV
Published
2009-10
Volume
30
Issue
10
Pages
475-487
ISSN
1471-4906 (ISSN-L)
OpenAlex
W1993197717
Cited by
1,318
References
6
Citations by year
2026: 56 · 2025: 59 · 2024: 72 · 2023: 64 · 2022: 74 · 2021: 79 · 2020: 86 · 2019: 84 · 2018: 90 · 2017: 94 · 2016: 89 · 2015: 80 · 2014: 82 · 2013: 107 · 2012: 98
FWCI
5.26
Type
journal article
Language
en
Open access
closed
Locations
  • Trends in Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
Keywords
endotoxin tolerance, lipopolysaccharide, monocytes, macrophages, sepsis, immunosuppression, MyD88 signaling, TRIF signaling, NF-κB, chromatin modification, microRNA, innate immunity, inflammation regulation
MeSH terms
Animals, Chromatin, Endotoxins, Humans, Immune Tolerance, Lymphocytes, Macrophages, Monocytes, Signal Transduction, Apoptosis, Systemic Inflammatory Response Syndrome, Receptors, Chemokine, MicroRNAs, Toll-Like Receptors

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