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Cyclooxygenase Inhibition in Sepsis: Is There Life after Death?
Prostaglandins are important mediators and modulators of the inflammatory response to infection. The prostaglandins participate in the pathogenesis of hemodynamic collapse, organ failure, and overwhelming inflammation that characterize severe sepsis and shock. In light of this, cyclooxygenase (COX)...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361325/ https://www.ncbi.nlm.nih.gov/pubmed/22665954 http://dx.doi.org/10.1155/2012/696897 |
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author | Aronoff, David M. |
author_facet | Aronoff, David M. |
author_sort | Aronoff, David M. |
collection | PubMed |
description | Prostaglandins are important mediators and modulators of the inflammatory response to infection. The prostaglandins participate in the pathogenesis of hemodynamic collapse, organ failure, and overwhelming inflammation that characterize severe sepsis and shock. In light of this, cyclooxygenase (COX) inhibiting pharmacological agents have been extensively studied for their capacity to ameliorate the aberrant physiological and immune responses during severe sepsis. Animal models of sepsis, using the systemic administration of pathogen-associated molecular patterns (PAMPs) or live pathogens, have been used to examine the effectiveness of COX inhibition as a treatment for severe sepsis. These studies have largely shown beneficial effects on mortality. However, human studies have failed to show clinical utility of COX inhibitor treatment in severely septic patients. Why this approach “worked” in animals but not in humans might reflect differences in the controlled nature of animal investigations compared to human studies. This paper contrasts the impact of COX inhibitors on mortality in animal models of sepsis and human studies of sepsis and examines potential reasons for differences between these two settings. |
format | Online Article Text |
id | pubmed-3361325 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-33613252012-06-04 Cyclooxygenase Inhibition in Sepsis: Is There Life after Death? Aronoff, David M. Mediators Inflamm Review Article Prostaglandins are important mediators and modulators of the inflammatory response to infection. The prostaglandins participate in the pathogenesis of hemodynamic collapse, organ failure, and overwhelming inflammation that characterize severe sepsis and shock. In light of this, cyclooxygenase (COX) inhibiting pharmacological agents have been extensively studied for their capacity to ameliorate the aberrant physiological and immune responses during severe sepsis. Animal models of sepsis, using the systemic administration of pathogen-associated molecular patterns (PAMPs) or live pathogens, have been used to examine the effectiveness of COX inhibition as a treatment for severe sepsis. These studies have largely shown beneficial effects on mortality. However, human studies have failed to show clinical utility of COX inhibitor treatment in severely septic patients. Why this approach “worked” in animals but not in humans might reflect differences in the controlled nature of animal investigations compared to human studies. This paper contrasts the impact of COX inhibitors on mortality in animal models of sepsis and human studies of sepsis and examines potential reasons for differences between these two settings. Hindawi Publishing Corporation 2012 2012-05-14 /pmc/articles/PMC3361325/ /pubmed/22665954 http://dx.doi.org/10.1155/2012/696897 Text en Copyright © 2012 David M. Aronoff. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Aronoff, David M. Cyclooxygenase Inhibition in Sepsis: Is There Life after Death? |
title | Cyclooxygenase Inhibition in Sepsis: Is There Life after Death? |
title_full | Cyclooxygenase Inhibition in Sepsis: Is There Life after Death? |
title_fullStr | Cyclooxygenase Inhibition in Sepsis: Is There Life after Death? |
title_full_unstemmed | Cyclooxygenase Inhibition in Sepsis: Is There Life after Death? |
title_short | Cyclooxygenase Inhibition in Sepsis: Is There Life after Death? |
title_sort | cyclooxygenase inhibition in sepsis: is there life after death? |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361325/ https://www.ncbi.nlm.nih.gov/pubmed/22665954 http://dx.doi.org/10.1155/2012/696897 |
work_keys_str_mv | AT aronoffdavidm cyclooxygenaseinhibitioninsepsisistherelifeafterdeath |