Advanced age exacerbates the pulmonary inflammatory response after lipopolysaccharide exposure
Advanced age exacerbates the pulmonary inflammatory response after lipopolysaccharide exposure
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DOI：
10.1097/01.ccm.0000251639.05135.e0
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发表时间：
2007-01-01
影响因子：
8.8
通讯作者：
Kovacs, Elizabeth J.
中科院分区：
文献类型：
--
作者：
Gomez, Christian R.;Hirano, Stefanie;Kovacs, Elizabeth J.
客观的。老年人口因受伤或感染并发症（例如急性肺损伤）而面临更高的死亡风险。本研究的目的是分析年轻和老年小鼠服用脂多糖后的肺部炎症反应。设计：前瞻性对照实验室研究。设置：动物资源设施和研究实验室。受试者。年轻（2-3 个月大）和老年（18-20 个月大）雌性 BALB/c 小鼠。干预措施。动物腹腔注射源自铜绿假单胞菌的脂多糖。对照小鼠仅接受盐水。 24小时后，处死小鼠。通过组织学和髓过氧化物酶活性评估肺中性粒细胞浸润。通过酶联免疫吸附测定评估 CXC 趋化因子、单核细胞炎症蛋白 2 和 KC 以及细胞因子、肿瘤坏死因子 α 和白细胞介素 1 β 的肺部水平。测量和主要结果。与给予脂多糖的年轻小鼠相比，给予脂多糖的老年小鼠的肺中性粒细胞浸润高出六倍，髓过氧化物酶活性水平高出三倍。与年轻小鼠相比，给予脂多糖的老年小鼠肺部单核细胞炎症蛋白 2 和 KC 的水平显着升高。还分析了肺中肿瘤坏死因子-α 和 intedeukin-1 β 的水平。脂多糖治疗后，年轻和老年动物肺部的肿瘤坏死因子-α水平没有差异，但老年组肺部的interieukin-1β水平高出两倍。这些数 老年受到炎症性侮辱。
Objective. The aged population is at a higher risk of mortality as a result of complications of injury or infection, such as acute lung injury. The objective of this study was to analyze pulmonary inflammatory responses in young and aged mice after administration of lipopolysaccharide.Design: Prospective, controlled laboratory study.Setting: Animal resource facilities and research laboratory.Subjects. Young (2-3 months old) and aged (18-20 months old) female BALB/c mice.Interventions. Animals received intraperitoneal injection of lipopolysaccharide derived from Pseudomonas aeruginosa. Control mice received saline alone. After 24 hrs, mice were killed. Pulmonary neutrophil infiltration was assessed histologically and by myeloperoxidase activity. Pulmonary levels of the CXC chemokines, monocyte inflammatory protein-2 and KC, and cytokines, tumor necrosis factor-alpha and interleukin-1 beta, were assessed by enzyme-linked immunosorbent assay.Measurements and Main Results. Lungs of aged mice given lipopolysaccharide showed a six-fold higher neutrophil infiltration and three-fold higher level of myeloperoxidase activity than lungs of young mice given lipopolysaccharide. Pulmonary levels of monocyte inflammatory protein-2 and KC were significantly higher in the lungs of aged mice given lipopolysaccharide, compared with younger mice. Levels of tumor necrosis factor-alpha and intedeukin-1 beta in the lung were analyzed as well. After lipopolysaccharide treatment, there was no difference in the level of tumor necrosis factor-alpha in lungs of young and aged animals, but interieukin-1 beta was two-fold higher in the lungs of the aged group. These data suggest that at this time point, interieukin-1 beta may contribute to the higher production of CXC chemokines observed in lungs of aged mice vs. young mice receiving lipopolysaccharide.Conclusions: The hyperreactive systemic inflammatory response seen in aged individuals after lipopolysaccharide administration is accompanied by an exacerbated pulmonary inflammatory response, which may contribute to the higher mortality seen in the aged given an inflammatory insult.