Pediatric Pulmonology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Immunobiology. 2011 Aug;216(8):901-8. doi: 10.1016/j.imbio.2011.02.003. Epub 2011 Feb 22.
Following any acute irritation lung function declines rapidly. Reasons for pulmonary deterioration in humans had been attributed to the action of either interleukin-6 or interleukin-8 in the lungs.
The present study investigates the association between immune response and decline in lung function in a murine bacterial lung infection model.
Upon intratracheal inoculation of C57BL/6J mice with a sublethal dose of Pseudomonas aeruginosa lung function, cytokine, chemokine and cytometry in bronchoalveolar lavage fluid, bacterial counts and lung histology was assessed at 2, 4, 6, 8, 10, 12, 18, 24, 48, 72, 96 and 120 h post inoculation.
Lung function measured by non-invasive head-out spirometry decreased most strongly between 6 and 10 h post inoculation and required up to 72 h to recover for selected parameters. CFU counts in the lungs peaked at 4h post inoculation with subsequent decline until at 24-48 h post inoculation background levels were reached. Cytokine and chemokine responses could be separated into an early pro-inflammatory phase (2-8h post inoculation; mainly tumor-necrosis factor α (TNFα) and interleukin-1α driven) and a late anti-inflammatory resolution phase (starting at 24h post inoculation; mainly interleukin-10 and interleukin-4 driven). Interleukin-6 levels correlated with the deterioration of lung function. Lung histology showed maximal changes in terms of inflammation and edema between 24 and 48 h post inoculation.
In summary, elevated interleukin-6, high local neutrophil counts and lung edema were found to be the most characteristic signs of the transient period of deterioration of lung function.
急性刺激后，肺功能迅速下降。人类肺部恶化的原因归因于白细胞介素-6 或白细胞介素-8 在肺部的作用。
本研究旨在探讨免疫反应与小鼠细菌性肺部感染模型中肺功能下降之间的关系。
通过气管内接种亚致死剂量铜绿假单胞菌，评估 C57BL/6J 小鼠肺功能、支气管肺泡灌洗液中的细胞因子、趋化因子和细胞计数、细菌计数和肺组织学，在接种后 2、4、6、8、10、12、18、24、48、72、96 和 120 小时。
通过非侵入性头出式肺活量计测量的肺功能在接种后 6 至 10 小时内下降最为明显，某些参数需要长达 72 小时才能恢复。肺部 CFU 计数在接种后 4 小时达到峰值，随后下降，直到 24-48 小时后达到背景水平。细胞因子和趋化因子反应可分为早期促炎期（接种后 2-8 小时；主要由肿瘤坏死因子-α（TNFα）和白细胞介素-1α驱动）和晚期抗炎消退期（接种后 24 小时开始；主要由白细胞介素-10 和白细胞介素-4 驱动）。白细胞介素-6 水平与肺功能恶化相关。肺组织学显示在接种后 24 至 48 小时之间炎症和水肿变化最大。
总之，发现白细胞介素-6 升高、局部中性粒细胞计数增加和肺水肿是肺功能短暂恶化的最特征性表现。
