Department of Environmental, Agricultural, and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Nutrients. 2012 Jul;4(7):695-710. doi: 10.3390/nu4070695. Epub 2012 Jul 4.
Alcohol exposure is associated with increased lung infections and decreased mucociliary clearance. Occupational workers exposed to dusts from concentrated animal feeding operations (CAFOs) are at risk for developing chronic inflammatory lung diseases. Agricultural worker co-exposure to alcohol and organic dust has been established, although little research has been conducted on the combination effects of alcohol and organic dusts on the lung. Previously, we have shown in a mouse model that exposure to hog dust extract (HDE) collected from a CAFO results in the activation of protein kinase C (PKC), elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6), and the development of significant lung pathology. Because alcohol blocks airway epithelial cell release of IL-6 in vitro, we hypothesized that alcohol exposure would alter mouse lung inflammatory responses to HDE. To test this hypothesis, C57BL/6 mice were fed 20% alcohol or water ad libitum for 6 weeks and treated with 12.5% HDE by intranasal inhalation method daily during the final three weeks. Bronchoalveolar lavage fluid (BALF), tracheas and lungs were collected. HDE stimulated a 2-4 fold increase in lung and tracheal PKCε (epsilon) activity in mice, but no such increase in PKCε activity was observed in dust-exposed mice fed alcohol. Similarly, alcohol-fed mice demonstrated significantly less IL-6 in lung lavage in response to dust than that observed in control mice instilled with HDE. TNFα levels were also inhibited in the alcohol and HDE-exposed mouse lung tissue as compared to the HDE only exposed group. HDE-induced lung inflammatory aggregates clearly present in the tissue from HDE only exposed animals were not visually detectable in the HDE/alcohol co-exposure group. Statistically significant weight reductions and 20% mortality were also observed in the mice co-exposed to HDE and alcohol. These data suggest that alcohol exposure depresses the ability of the lung to activate PKCε-dependent inflammatory pathways to environmental dust exposure. These data also define alcohol as an important co-exposure agent to consider in the study of inhalation injury responses.
酒精暴露与肺部感染增加和黏液纤毛清除功能下降有关。接触来自集中式动物饲养场（CAFO）的粉尘的职业工人有患慢性炎症性肺部疾病的风险。农业工人同时接触酒精和有机粉尘的情况已经得到证实，尽管对酒精和有机粉尘对肺部的联合作用的研究很少。以前，我们在小鼠模型中表明，暴露于从 CAFO 收集的猪尘提取物（HDE）会导致蛋白激酶 C（PKC）的激活，升高包括白细胞介素 6（IL-6）在内的灌洗液细胞因子/趋化因子，并导致显著的肺部病理学发展。因为酒精在体外阻止气道上皮细胞释放 IL-6，所以我们假设酒精暴露会改变小鼠肺部对 HDE 的炎症反应。为了验证这一假设，C57BL/6 小鼠自由饮用 20%的酒精或水 6 周，并在最后 3 周每天通过鼻内吸入法用 12.5%的 HDE 处理。收集支气管肺泡灌洗液（BALF）、气管和肺。HDE 刺激小鼠肺部和气管中的 PKCε（epsilon）活性增加 2-4 倍，但在酒精暴露的粉尘暴露小鼠中未观察到这种 PKCε 活性增加。同样，与仅用 HDE 处理的对照组小鼠相比，酒精喂养的小鼠对粉尘的反应中肺灌洗液中的 IL-6 明显减少。与仅用 HDE 暴露的组相比，TNFα 水平在酒精和 HDE 暴露的小鼠肺组织中也受到抑制。仅用 HDE 暴露的动物组织中明显存在的 HDE 诱导的肺部炎症聚集物在 HDE/酒精共暴露组中肉眼不可见。在同时暴露于 HDE 和酒精的小鼠中还观察到体重显著减轻和 20%的死亡率。这些数据表明，酒精暴露抑制了肺部激活 PKCε 依赖性炎症途径对环境粉尘暴露的能力。这些数据还将酒精定义为在吸入性损伤反应研究中需要考虑的重要共同暴露剂。
