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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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Detalles Bibliográficos
Autor principal: Aronoff, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
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.
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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.
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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
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