Dhanireddy Shireesha, Altemeier William A, Matute-Bello Gustavo, O'Mahony D Shane, Glenny Robb W, Martin Thomas R, Liles W Conrad
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98103, USA.
Lab Invest. 2006 Aug;86(8):790-9. doi: 10.1038/labinvest.3700440. Epub 2006 Jul 3.
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 (C57Bl/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.
机械通气（MV）常用于治疗患有呼吸衰竭的重症患者。机械通气（MV）的一个主要并发症是呼吸机相关性肺炎（VAP）的发生，其中金黄色葡萄球菌是一种主要病原体。此外，先前的研究表明，MV可能是急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）发生发展的一个重要辅助因素。在自主呼吸小鼠（C57Bl/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是否会促进ALI和/或全身炎症的发展。MV与细菌的联合作用显著增加了中性粒细胞向支气管肺泡灌洗液（BALF）中的流入，增强了促炎细胞因子KC、MIP-2、TNF-α和IL-6在肺部的产生，并增加了肺泡-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表达，这与肺外肝肾功能障碍有关。令人惊讶的是，MV并未影响肺部细菌清除及肺外细菌播散。这些数据表明，MV会加剧机体对细菌的肺部和全身炎症反应，并促进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播散。
