Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Maywood, IL, USA.
Shock. 2011 Apr;35(4):403-10. doi: 10.1097/SHK.0b013e31820217c9.
Pulmonary infections are a major cause of mortality in the critically ill burn patient. Alcohol consumption before burn increases the risk of pulmonary infection. Previously, we have shown an elevated mortality and lung pathology in mice given ethanol before burn and intratracheal infection relative to controls. Here we examine the cellular composition at 24 and 48 h in the circulation and the alveoli of infected mice given alcohol and burn. At 24 h after injury, blood neutrophils obtained from mice exposed to ethanol before burn and infection were 2-fold above those of the experimental controls (P < 0.05). By 48 h, the number of circulating neutrophils decreased and was comparable to levels found in untreated animals. Moreover, at 24 h, bronchoalveolar lavage cells obtained from all treatment groups had similar frequencies and contained 80% neutrophils regardless of treatment. In contrast, the following day, neutrophils were elevated 2-fold only in the alveoli of infected burn animals and 5-fold when ethanol preceded the injury (P < 0.05). These data were confirmed by immunofluorescence microscopy using a neutrophil-specific marker (P < 0.05). Levels of neutrophil chemoattractants, KC and macrophage inflammatory protein 2, and the cytokine, IL-1β, were 2-fold greater in the lungs of infected mice given burn, regardless of ethanol exposure, relative to infected sham injured animals (P < 0.05). Like the number of neutrophils, by the second day after injury, KC and macrophage inflammatory protein 2 remained 5-fold higher in the animals given ethanol, burn, and infection, when compared with other groups (P < 0.05). A similar pattern was seen for pulmonary levels of IL-1β (P < 0.05). Additionally, a reduction in neutrophil apoptosis was observed at the 24-h time point in infected mice exposed to ethanol and burn (P < 0.05). Targeting proinflammatory mediators in mice exposed to ethanol before burn and infection may help alleviate prolonged neutrophil accumulation in the lungs.
肺部感染是重症烧伤患者死亡的主要原因。烧伤前饮酒会增加肺部感染的风险。此前，我们已经证明，与对照组相比，烧伤前给予乙醇并气管内感染的小鼠死亡率升高，肺部病理改变更为严重。在此，我们检测了感染小鼠在循环系统和肺泡中 24 小时和 48 小时的细胞组成。在损伤后 24 小时，与实验对照组相比，暴露于乙醇的烧伤和感染小鼠的血液中性粒细胞增加了 2 倍（P<0.05）。到 48 小时时，循环中性粒细胞数量减少，与未处理动物的水平相当。此外，在 24 小时时，来自所有治疗组的支气管肺泡灌洗液细胞具有相似的频率，并且无论治疗如何，其中 80%都是中性粒细胞。相比之下，仅在感染烧伤动物的肺泡中，第二天中性粒细胞增加了 2 倍，而在乙醇先于损伤时增加了 5 倍（P<0.05）。这些数据通过使用中性粒细胞特异性标志物的免疫荧光显微镜得到了证实（P<0.05）。无论是否暴露于乙醇，与感染假手术损伤动物相比，感染烧伤的小鼠肺中中性粒细胞趋化因子 KC 和巨噬细胞炎症蛋白 2 以及细胞因子 IL-1β 的水平均增加了 2 倍（P<0.05）。与中性粒细胞数量一样，在损伤后第二天，与其他组相比，给予乙醇、烧伤和感染的动物的 KC 和巨噬细胞炎症蛋白 2 仍高 5 倍（P<0.05）。IL-1β 的肺水平也出现了类似的模式（P<0.05）。此外，在感染的乙醇暴露的小鼠中，在 24 小时时间点观察到中性粒细胞凋亡减少（P<0.05）。在乙醇暴露前烧伤和感染的小鼠中靶向促炎介质可能有助于减轻肺部中性粒细胞的长期积聚。
