Ventilation-induced chemokine and cytokine release is associated with activation of nuclear Factor-κB and is blocked by steroids
Ventilation-induced chemokine and cytokine release is associated with activation of nuclear Factor-κB and is blocked by steroids
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DOI：
10.1164/ajrccm.163.3.2003001
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发表时间：
2001-03-01
影响因子：
24.7
通讯作者：
Uhlig, S
中科院分区：
文献类型：
--
作者：
Held, HD;Boettcher, S;Uhlig, S
最近的临床试验表明，减少通气容量可提高急性呼吸窘迫综合征（ARDS）患者的生存率。这些研究表明，肺部过度膨胀会导致免疫系统过度激活。本研究调查了这样一种假设，即潮汐量增加的通气导致的早期反应与刺激ARDS的主要危险因素之一：细菌脂多糖（LPS）引起的早期反应相似。因此，我们比较了通气（-10 cm H2O或-25 cm H2O吸气末压力）和LPS（50马克杯/毫升）对BALB/C小鼠离体灌注肺核因子(NF)-kappaB活化、趋化因子释放和细胞因子释放的影响。我们发现LPS和-25 cm H2O通气（过度通气；OV）都会导致NF-kappaB易位，而类固醇地塞米松预处理可以消除NF-kappaB易位。此外，两种治疗均导致灌注液中α -趋化因子（巨噬细胞炎性蛋白[MIP]-2； KC）、β -趋化因子（巨噬细胞趋化蛋白-1；MlP-1 α）和细胞因子（肿瘤坏死因子- α、白细胞介素-6）水平的相似升高，而地塞米松预处理在很大程度上阻止了这些升高。在LPS抗性C3H/HeJ小鼠中，只有OV而非LPS引起NF-KB的易位和MIP-2的释放。我们得出结论，OV引起的早期炎症反应类似于LPS引起的炎症反应（即NF-kappaB易位和促炎介质的释放）。OV引起的NF-kappaB易位似乎与toll样受体4无关，与呼吸机引入的LPS污染无关。我们的数据进一步表明类固醇可能被认为是人工机械通气期间的辅助治疗。
Recent clinical trials have shown that the survival of patients with acute respiratory distress syndrome (ARDS) is improved by ventilation with reduced volumes. These studies suggested that overinflation of the lungs causes overactivation of the immune system. The present study investigated the hypothesis that ventilation with increased tidal volumes results in early responses similar to those caused by stimulation with one of the major risk factors for ARDS: bacterial lipopolysaccharide (LPS). We therefore compared the effects of ventilation (-10 cm H2O or -25 cm H2O end-inspiratory pressure) and LPS (50 mug/ml) on nuclear factor (NF)-kappaB activation, chemokine release, and cytokine release in isolated perfused lungs obtained from BALB/C mice. We found that both LPS and ventilation with -25 cm H2O (overventilation; OV) caused translocation of NF-kappaB, which was abolished by pretreatment with the steroid dexamethasone. Furthermore, both treatments resulted in similar increases in perfusate levels of alpha -chemokines (macrophage inflammatory protein; [MIP]-2; KC), beta -chemokines (macrophage chemotactic protein-1; MlP-1 alpha), and cytokines (tumor necrosis factor-alpha, interleukin-6), which were largely prevented by dexamethasone pretreatment. In LPS-resistant C3H/HeJ mice, only OV, and not LPS, caused translocation of NF-KB and release of MIP-2. We conclude that OV evokes early inflammatory responses similar to those evoked by LPS (i.e., NF-kappaB translocation and release of proinflammatory mediators). The NF-kappaB translocation elicited by OV appears to be independent of Toll-like receptor 4 and not due to LPS contamination introduced by the ventilator. Our data further suggest that steroids might be considered as a subsidiary treatment during artificial mechanical ventilation.