Cyclooxygenase inhibition in sepsis: is there life after death?
Cyclooxygenase inhibition in sepsis: is there life after death?
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DOI：
10.1155/2012/696897
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发表时间：
2012
影响因子：
4.6
通讯作者：
Aronoff DM
中科院分区：
文献类型：
--
作者：
Aronoff DM
前列腺素是感染炎症反应的重要介质和调节剂。前列腺素参与血流动力学崩溃、器官衰竭和严重炎症的发病机制，这些炎症是严重脓毒症和休克的特征。鉴于此，环氧合酶（COX）抑制药物因其改善严重脓毒症期间异常生理和免疫反应的能力而被广泛研究。使用病原体相关分子模式 (PAMP) 或活病原体的全身给药的脓毒症动物模型已被用来检查 COX 抑制作为治疗严重脓毒症的有效性。这些研究在很大程度上表明了对死亡率的有益影响。然而，人体研究未能显示 COX 抑制剂治疗严重脓毒症患者的临床效用。为什么这种方法在动物中“有效”，但在人类中无效，可能反映了动物研究与人类研究相比在受控性质上的差异。本文对比了 COX 抑制剂对脓毒症动物模型和人类脓毒症研究中死亡率的影响，并探讨了这两种情况之间差异的潜在原因。
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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影响因子：
9
作者：
FINK, MP;MACVITTIE, TJ;CASEY, LC
通讯作者：
CASEY, LC
影响因子：
4.8
作者：
Ejima, K;Layne, MD;Perrella, MA
通讯作者：
Perrella, MA
影响因子：
4.4
作者：
Aronoff, David M.;Lewis, Casey;Mancuso, Peter
通讯作者：
Mancuso, Peter
影响因子：
3.7
作者：
Celik, I;Akbulut, A;Felek, S
通讯作者：
Felek, S
影响因子：
5.2
作者：
Fink, MP
通讯作者：
Fink, MP