Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia
Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia
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DOI：
10.1172/jci7124
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发表时间：
1999-09-01
影响因子：
15.9
通讯作者：
Wiener-Kronish, JP
中科院分区：
文献类型：
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作者：
Kurahashi, K;Kajikawa, O;Wiener-Kronish, JP
在家兔模型中研究了铜绿假单胞菌肺炎后发生脓毒性休克的发病机制。将细胞毒性铜绿假单胞菌菌株PA 103空气滴注到家兔体内导致一致的肺泡上皮损伤、进行性菌血症和脓毒性休克。无细胞毒性的同基因突变株（PA 103 Δ UT），这是有缺陷的III型分泌毒素的生产，肺滴注，没有引起全身炎症反应或感染性休克，尽管在肺部的强有力的炎症反应。尽管动物存在菌血症，但静脉注射PA 103未引起休克或TNF-α升高。全身给予抗TNF-α血清或重组人IL-10改善了灌注PA 103的动物的败血性休克和菌血症。只有在肺泡上皮损伤的情况下，肺中滴注的放射性标记的TNF-α才显著泄漏到循环中。我们的结论是，肺泡上皮细胞的损伤允许释放的促炎介质进入循环，主要负责感染性休克。我们的研究结果表明，在肺中的炎症介质的区室化的重要性，以及细菌细胞毒素在导致肺泡上皮细胞损伤的铜绿假单胞菌肺炎急性感染性休克的发病机制中的关键作用。
The pathogenesis of septic shock occurring after Pseudomonas aeruginosa pneumonia was studied in a rabbit model. The airspace instillation of the cytotoxic P. aeruginosa strain PA103 into the rabbit caused a consistent alveolar epithelial injury, progressive bacteremia, and septic shock. The lung instillation of a noncytotoxic, isogenic mutant strain (PA103 Delta UT), which is defective for production of type III secreted toxins, did not cause either systemic inflammatory response or septic shock, despite a potent inflammatory response in the lung. The intravenous injection of PA103 did not cause shock or an increase in TNF-alpha, despite the fact that the animals were bacteremic. The systemic administration of either anti-TNF-alpha serum or recombinant human IL-10 improved both septic shock and bacteremia in the animals that were instilled with PA103. Radiolabeled TNF-alpha instilled in the lung significantly leaked into the circulation only in the presence of alveolar epithelial injury. We conclude that injury to the alveolar epithelium allows the release of proinflammatory mediators into the circulation that are primarily responsible for septic shock. Our results demonstrate the importance of compartmentalization of inflammatory mediators in the lung, and the crucial role of bacterial cytotoxins in causing alveolar epithelial damage in the pathogenesis of acute septic shock in P. aeruginosa pneumonia.