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Cited by 151Sepsis Diagnosis and TreatmentImmune Response and InflammationInflammation biomarkers and pathways

Clinical detection of LPS and animal models of endotoxemia

Redl, Heinz, Bahrami, Soheyl, Schlag, Günther, Traber, Dan L.·1993·Immunobiology
DOI 10.1016/s0171-2985(11)80348-7
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Abstract

The interest in the study of endotoxemia in the clinical area has increased recently as a result of a) improved and simplified endotoxin determination e.g. chromogenic-kinetic microplate methods (also an improved blood sampling tool is available), b) incidence of sepsis has increased due to improvement in early (e.g. posttraumatic) survival, c) interest in and good evidence for gut translocation as a source of endotoxemia, d) agents have developed, which can antagonize endotoxins. There is evidence that patients with positive endotoxin test in the ICU have a higher incidence of organ failure. To study the pathophysiological consequences of endotoxemia and possible ways of intervention animal models are necessary. The choice of the experimental setting depends on the aim of the study e.g. whether prolonged observation is necessary in survival studies or whether hemodynamic variables have to be measured or whether therapeutic agents only crossreact with primates. Since LPS levels are quite low in clinical studies, an important factor for selection of a relevant animal might be LPS sensitivity, or the use of additional sensitization techniques e.g. galactosamine. Another important aspect in this context is whether LPS is given as bolus or infused up to several days. In this review the dose, time, and route of LPS administration is also discussed. For screening purposes rodents are usually used, or sometimes rabbits due to their higher LPS sensitivity. Another very sensitive animal model is the sheep, which can be chronically instrumented and as a specialty allows lung lymph drainage and thus studies of LPS effects on pulmonary permeability. Pigs are used for hemodynamic studies and often in therapeutical studies if species-specificity of the drug tested is not important, in cases where a large animal is necessary. Finally the non-human primates offer a number of advantages due to human-like physiology, due to the cross-reactivity of human assay systems and accordingly also cross-reactivity of human therapeutic agents. While the chimpanzee also shares the LPS sensitivity of humans, baboons are insensitive like rodents. Thus each model serves to provide some useful purpose and the selection must be made to meet the requirements of the specific questions to be asked, with special emphasis of the chosen endotoxin model on relevance for the human sepsis state.

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Authors
Redl, H., Bahrami, S., Schlag, G., & Traber, D. L.
Affiliations
  • Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA (AT)
  • Shriners Hospitals for Children - Galveston (US)
ORCID
Venue
Immunobiology
Publisher
Elsevier BV
Published
1993-04
Volume
187
Issue
3-5
Pages
330-345
ISSN
0171-2985 (ISSN-L)
DOI
10.1016/s0171-2985(11)80348-7
OpenAlex
W2060345460
Cited by
151
References
88
Citations by year
2026: 1 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 3
FWCI
6.42
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Immunobiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords
endotoxemia, lipopolysaccharide, animal models, sepsis, gut translocation, organ failure, sheep, pigs, non-human primates, baboons, chimpanzees, lung permeability, hemodynamics, endotoxin antagonists, endotoxin detection
MeSH terms
Animals, Disease Models, Animal, Endotoxins, Humans, Lipopolysaccharides, Toxemia, Bacteremia, Gram-Negative Bacterial Infections

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