The pulmonary and hepatic immune microenvironment and its contribution to the early systemic inflammation following blunt chest trauma
The pulmonary and hepatic immune microenvironment and its contribution to the early systemic inflammation following blunt chest trauma
复制标题
DOI：
10.1097/01.ccm.0000207343.53990.a8
复制
发表时间：
2006-04-01
影响因子：
8.8
通讯作者：
Knöferl, MW
中科院分区：
文献类型：
--
作者：
Perl, M;Gebhard, F;Knöferl, MW
目的：钝性胸部创伤后早期血浆细胞因子浓度升高。然而，这些调解人的地方来源定义不清。我们研究了钝性胸部创伤对不同隔室（肺组织、支气管肺泡灌洗液、肝组织、枯否细胞、血浆）中炎症介质环境的影响沿着创伤诱导的肺内皮屏障功能障碍的时间过程，以阐明潜在的关系。此外，我们还研究了IL-6的全身释放与IL-6气管内滴注的相关性。设计：前瞻性、随机、对照动物研究。实验对象：雄性C3 H/HeN小鼠，8-9周龄，n = 141。干预：用聚焦冲击波致钝性胸部创伤，静脉注射伊文思蓝，肺内滴注重组人白细胞介素-6。同时，支气管肺泡灌洗液中的白细胞介素-6、肿瘤坏死因子-α、巨噬细胞炎性蛋白-2、单核细胞趋化多肽-1和中性粒细胞/单核细胞积聚以及肺组织中的白细胞介素-6、单核细胞趋化多肽-1和髓过氧化物酶活性显著升高。这伴随着埃文斯蓝肺-血浆比率的一致升高。重组人白细胞介素-6，灌输intrathheal钝性胸部创伤前，在小鼠的血浆中检测到剂量依赖性的方式。此外，库普弗细胞白细胞介素-6、肿瘤坏死因子-α和白细胞介素-10的产生早在损伤后30分钟就显著增加。这些结果表明，早期增加的细胞因子浓度在肺中，特别是白细胞介素-6，是重要的介质源，因为它们的局部峰值与全身炎症反应相一致，并伴随着同时受损的肺内皮屏障功能。可以建立其局部和全身浓度之间的直接关系。此外，这是第一项研究表明，枯否细胞在钝性胸部创伤后早期被激活。
Objective: Blunt chest trauma is accompanied by an early increase in plasma cytokine concentrations. However, the local sources of these mediators are poorly defined. We investigated the impact of blunt chest trauma on the inflammatory mediator milieu in different compartments (lung tissue, bronchoalveolar lavage, liver tissue, Kupffer cells, plasma) along with the time course of trauma-induced pulmonary endothelial barrier dysfunction to elucidate potential relationships. In addition, the correlation between intratracheally instilled interleukin-6 and its systemic release were studied.Design: Prospective, randomized, controlled animal study.Setting. Basic science laboratory of a university affiliated level 1 trauma center.Subjects: Male C3H/HeN mice, 8-9 wks old, n = 141.Interventions: Blunt chest trauma induced by a focused blast wave, intravenous injection of Evans blue, and intratracheal instillation of recombinant human interleukin-6.Measurements and Main Results: Two hours after blunt chest trauma, plasma interleukin-6 was markedly increased. Simultaneously, interleukin-6, tumor necrosis factor-alpha, macrophage inflammatory protein-2, monocyte chemotactic polypeptide-1 and neutrophil/monocyte accumulation in bronchoalveolar lavage and interleukin-6, monocyte chemotactic polypeptide-1, and myeloperoxidase activity in lung tissue were significantly increased. This was accompanied by a coinciding elevation in the Evans blue lung-plasma ratio. Recombinant human interleukin-6, instilled intratracheally before blunt chest trauma, was detected in a dose-dependent manner in the plasma of the mice. Additionally, Kupffer cell interleukin-6, tumor necrosis factor-alpha, and interleukin-10 production was significantly augmented as early as 30 mins after the insult.Conclusions. These results indicate that early increased cytokine concentrations in the lung, particularly interleukin-6, are important mediator sources as their local peak coincides with the systemic inflammatory response and is accompanied by a simultaneous impaired function of the pulmonary endothelial barrier. A direct relationship between their local and systemic concentrations can be established. Furthermore, this is the first study to show that Kupffer cells are activated early after blunt chest trauma.