Septic shock and acute lung injury in rabbits with peritonitis - Failure of the neutrophil response to localized infection
Septic shock and acute lung injury in rabbits with peritonitis - Failure of the neutrophil response to localized infection
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DOI：
10.1164/ajrccm.163.1.9909034
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发表时间：
2001-01-01
影响因子：
24.7
通讯作者：
Martin, TR
中科院分区：
文献类型：
--
作者：
Matute-Bello, G;Frevert, CW;Martin, TR
本研究的主要目的是研究宿主对腹腔局部感染的反应与脓毒症和肺损伤的发生之间的机制。通过腹膜内接种含有10（8）、10（9）或10（10）cfu/凝块的埃希氏螺旋的纤维蛋白凝块感染家兔。监测生理学、细菌学和炎症反应，并在死后检查肺部。在108 cfu/血凝块剂量下，动物感染消退，109 cfu/血凝块剂量导致24 h持续感染，全身表现极轻微。相比之下，接种10（10）cfu/凝块导致快速致命的局部感染，脓毒性休克和肺损伤。感染性休克的发生与腹膜腔中可识别的多形核白细胞（PMN;中性粒细胞）的矛盾缺乏有关。在腹膜中的PMN的情况下，部分是由于溶解的腹膜内的PMN，因为腹腔液中含有游离的髓过氧化物酶和诱导的正常兔PMN在体外的快速死亡。虽然大多数动物成为菌血症，只有那些严重的全身炎症反应发展肺损伤。这些数据表明，控制细菌进入宿主的第一隔室中的感染是全身反应的关键决定因素。在细菌的阈值剂量以上，局部嗜中性粒细胞反应的失败是与有害的全身反应相关的关键机制。菌血症本身不足以引起肺损伤。肺损伤仅发生在严重的全身炎症反应和原发感染部位白细胞反应不足的情况下。
The major goal of this study was to investigate the mechanisms that link the host response to a local infection in the peritoneal cavity with the development of sepsis and lung injury. Rabbits were infected by intraperitoneal inoculation of fibrin clots containing Es-cherichia coil at 10(8), 10(9), or 10(10) cfu/clot. Physiologic, bacteriologic, and inflammatory responses were monitored, and the lungs were examined postmortem. At a dose of 108 cfu/clot the animals had resolving infection, and a dose of 109 cfu/clot resulted in persistent infection at 24 h, with minimal systemic manifestations. In contrast, inoculation of 10(10) cfu/clot resulted in rapidly lethal local infection, with septic shock and lung injury. The onset of septic shock was associated with a paradoxical lack of identifiable polymorphonuclear leukocytes (PMN; neutrophils) in the peritoneal cavity. The absence of PMN in the peritoneum was due in part to lysis of intraperitoneal PMN, because the peritoneal fluids contained free myeloperoxidase and induced rapid death of normal rabbit PMN in vitro. Although most animals became bacteremic, only those with a severe systemic inflammation response developed lung injury. These data show that control of an infection in the first compartment in which bacteria enter the host is a critical determinant of the systemic response. Above a threshold dose of bacteria, failure of the local neutrophil response is a key mechanism associated with deleterious systemic responses. Bacteremia alone is not sufficient to cause lung injury. Lung injury occurs only in the setting of a severe systemic inflammatory response and an inadequate leukocyte response at the primary site of infection.