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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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2012/696897 |
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| author | David M. Aronoff |
| author_facet | David M. Aronoff |
| author_sort | David M. Aronoff |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-737ee7a56c2045599a449f6a7af3b68b |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-737ee7a56c2045599a449f6a7af3b68b2025-02-03T05:46:47ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/696897696897Cyclooxygenase Inhibition in Sepsis: Is There Life after Death?David M. Aronoff0Division of Infectious Diseases, Department of Internal Medicine and Department of Microbiology and Immunology, Graduate Program in Immunology, Reproductive Sciences Program, the University of Michigan, Ann Arbor, MI 48109, USAProstaglandins 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.http://dx.doi.org/10.1155/2012/696897 |
| spellingShingle | David M. Aronoff Cyclooxygenase Inhibition in Sepsis: Is There Life after Death? Mediators of Inflammation |
| 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 |
| url | http://dx.doi.org/10.1155/2012/696897 |
| work_keys_str_mv | AT davidmaronoff cyclooxygenaseinhibitioninsepsisistherelifeafterdeath |