The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
EVALUATION OF ENDOTOXIN MODELS FOR THE STUDY OF SEPSIS
Abstract
Many strategies have been proposed for the treatment of sepsis, and most of the proposed treatment modalities have failed in clinical trials. Many of the previous treatment protocols called for blocking the activity of a single, clearly defined mediator. The underlying hypothesis was that sepsis induced a specific mediator that then caused organ injury and death. This simple, linear reasoning was frequently based on cytokines that were defined using endotoxin models of sepsis. The endotoxin models were widely used to study the pathophysiology of sepsis and were felt to adequately reproduce the full spectrum of inflammatory changes observed in patients with sepsis. Based on mortality and hematologic changes, these assumptions appeared justified. As the models were examined more closely, and directly compared with focus of infection models that more accurately portray the changes in sepsis, it became apparent that the endotoxin models did not accurately mimic the patient with sepsis. In the endotoxin models, the explosive release of cytokines into the circulating blood volume was reproducibly found regardless of the species studied (human, primate, pig, rat, or mouse). This lead to a series of anticytokine sepsis trials, all of which failed. The cytokine response in focus of infection models, such as that induced by cecal ligation and puncture, was examined and found to be more similar to that observed in patients with sepsis. When cytokine inhibitor strategies were used in the cecal ligation and puncture model, they were also generally found to lack efficacy. Compounds that have been shown to be effective at reducing mortality in endotoxin models should be re-evaluated in more clinically relevant models of sepsis.
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Cites
Early goal-directed therapy in the treatment of severe sepsis and septic shock
Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., & Tomlanovich, M. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa010307 · Cited by 10,743
The epidemiology of sepsis in the United States from 1979 through 2000
Martin, G. S., Mannino, D. M., Eaton, S., & Moss, M. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022139 · Cited by 5,841
An endotoxin-induced serum factor that causes necrosis of tumors
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Shock and Tissue Injury Induced by Recombinant Human Cachectin
Tracey, K. J., Beutler, B., Lowry, S. F., Merryweather, J., Wolpe, S., Milsark, I. W., Hariri, R. J., Fahey, T. J., Zentella, A., Albert, J. D., et al. (1986) · Science · doi:10.1126/science.3764421 · Cited by 2,549
Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia
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“The second line of evidence that TNFa was an important mediator in the pathogenesis of sepsis was found in the preclinical experiments that showed that blockade of TNFa would improve outcome in experimental animals given bolus injections of endotoxin or live bacteria (21, 23).”
BackgroundElliott, M. J., Maini, R. N., Feldmann, M., Kalden, J. R., Antoni, C., Smolen, J. S., Leeb, B., Breedveld, F. C., Macfarlane, J. D., Bijl, J. A., et al. (1994) · The Lancet · doi:10.1016/s0140-6736(94)90628-9 · Cited by 1,682
Detection of circulating tumor necrosis factor after endotoxin administration
Michie, H. R., Manogue, K. R., Spriggs, D. R., Revhaug, A., O'Dwyer, S., Dinarello, C. A., Cerami, A., Wolff, S. M., & Wilmore, D. W. (1988) · New England Journal of Medicine · doi:10.1056/nejm198806093182301 · Cited by 1,677 · cited 2×
“First, endotoxin infusion into experimental animals (13, 14), or human volunteers (15, 16) causes the release of massive quantities of proinflammatory cytokines.”
BackgroundCarter, D. B., Deibel, M. R., Dunn, C. J., Tomich, C.-S. C., Laborde, A. L., Slightom, J. L., Berger, A. E., Bienkowski, M. J., Sun, F. F., McEwan, R. N., et al. (1990) · Nature · doi:10.1038/344633a0 · Cited by 601
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Cited by
The inflammatory response in sepsis
Bosmann, M., & Ward, P. A. (2013) · Trends in Immunology · doi:10.1016/j.it.2012.09.004 · Cited by 558
Self-citationThe disconnect between animal models of sepsis and human sepsis
Rittirsch, D., Hoesel, L. M., & Ward, P. A. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0806542 · Cited by 406
Self-citationAnimal models of sepsis: Why does preclinical efficacy fail to translate to the clinical setting?
Dyson, A., & Singer, M. (2009) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181922bd3 · Cited by 273
Metadata
- Authors
- Remick, D. G., & Ward, P. A.
- Venue
- Shock
- Published
- 2005-12
- Volume
- 24
- Issue
- Supplement 1
- Pages
- 7-11
- ISSN
- 1073-2322 (ISSN-L)
- OpenAlex
- W2012110029
- Cited by
- 202
- References
- 10
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- closed
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- Remick, D. G., & Ward, P. A. (2005). EVALUATION OF ENDOTOXIN MODELS FOR THE STUDY OF SEPSIS. Shock. https://doi.org/10.1097/01.shk.0000191384.34066.85
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
