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Cyclooxygenase Inhibition in Sepsis: Is There Life after Death?

Authors :
David M. Aronoff
Source :
Mediators of Inflammation, Vol 2012 (2012)
Publication Year :
2012
Publisher :
Hindawi Limited, 2012.

Abstract

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.

Subjects

Subjects :
Pathology
RB1-214

Details

Language :
English
ISSN :
09629351 and 14661861
Volume :
2012
Database :
Directory of Open Access Journals
Journal :
Mediators of Inflammation
Publication Type :
Academic Journal
Accession number :
edsdoj.737ee7a56c2045599a449f6a7af3b68b
Document Type :
article
Full Text :
https://doi.org/10.1155/2012/696897