Mechanical ventilation induces inflammation, lung injury, and extra-pulmonary organ dysfunction in experimental pneumonia
Mechanical ventilation induces inflammation, lung injury, and extra-pulmonary organ dysfunction in experimental pneumonia
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DOI：
10.1038/labinvest.3700440
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发表时间：
2006-08-01
影响因子：
5
通讯作者：
Liles, W. Conrad
中科院分区：
文献类型：
--
作者：
Dhanireddy, Shireesha;Altemeier, William A.;Liles, W. Conrad
机械通气（MV）是治疗呼吸衰竭危重患者的常用手段。机械通气（MV）的主要并发症是呼吸机相关性肺炎（VAP）的发展，其中金黄色葡萄球菌是一个突出的病原体。此外，既往研究表明，MV可能是急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）发生的重要辅助因子。在自主呼吸小鼠（C57BI/6）或机械通气小鼠中诱导金黄色葡萄球菌肺部感染，以确定MV是否有助于ALI和/或全身性炎症的发生。MV和细菌的结合显著增加了中性粒细胞流入支气管肺泡灌洗液（BALF），增加了肺中促炎细胞因子KC、MIP-2、tnf - α和IL-6的产生，增加了肺泡毛细血管对蛋白质的通透性。MV还诱导外周血中促炎细胞因子的表达，与肺外肝肾功能障碍有关。令人惊讶的是，肺内细菌清除率和肺外细菌播散不受MV的影响。这些数据表明，MV加重了肺部和全身炎症对细菌的反应，并有助于ALI和多器官功能障碍综合征的发病机制，而不一定影响细菌清除或肺外细菌传播。
Mechanical ventilation ( MV) is frequently employed for the management of critically ill patients with respiratory failure. A major complication of mechanical ventilation ( MV) is the development of ventilator-associated pneumonia ( VAP), in which Staphylococcus aureus is a prominent pathogen. Moreover, previous studies suggest that MV may be an important cofactor in the development of acute lung injury ( ALI) and the acute respiratory distress syndrome ( ARDS). S. aureus pulmonary infection was induced in spontaneously breathing mice ( C57BI/6) or mechanically ventilated mice to determine whether MV contributes to the development of ALI and/or systemic inflammation. The combination of MV and bacteria significantly increased the influx of neutrophils into bronchoalveolar lavage fluid ( BALF), augmented pulmonary production of the proinflammatory cytokines KC, MIP-2, TNF-alpha, and IL-6, and increased alveolar-capillary permeability to proteins. MV also induced proinflammatory cytokine expression in peripheral blood, associated with extrapulmonary hepatic and renal dysfunction. Surprisingly, bacterial clearance in the lungs and extrapulmonary bacterial dissemination was not affected by MV. These data indicate that MV exacerbates both pulmonary and systemic inflammation in response to bacteria and contributes to the pathogenesis of both ALI and the multiple organ dysfunction syndrome, without necessarily affecting bacterial clearance or extra-pulmonary bacterial dissemination.