Kobbe Philipp, Stoffels Burkhard, Schmidt Joachim, Tsukamoto Takeshi, Gutkin Dmitry W, Bauer Anthony J, Pape Hans-Christoph
Department of Orthopaedic Surgery, University of Pittsburgh, Kaufmann Medical Building, Suite 1010, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA.
Cytokine. 2009 Jan;45(1):26-31. doi: 10.1016/j.cyto.2008.10.004. Epub 2008 Nov 17.
In hemorrhagic shock and trauma, patients are prone to develop systemic inflammation with remote organ dysfunction, which is thought to be caused by pro-inflammatory mediators. This study investigates the role of the immuno-modulatory cytokine IL-10 in the development of organ dysfunction following hemorrhagic shock. Male C57/BL6 and IL-10 KO mice were subjected to volume controlled hemorrhagic shock for 3h followed by resuscitation. Animals were either sacrificed 3 or 24h after resuscitation. To assess systemic inflammation, serum IL-6, IL-10, KC, and MCP-1 concentrations were measured with the Luminex multiplexing platform; acute lung injury (ALI) was assessed by pulmonary myeloperoxidase (MPO) activity and lung histology and acute liver injury was assessed by hepatic MPO activity, hepatic IL-6 levels, and serum ALT levels. There was a trend towards increased IL-6 and KC serum levels 3h after resuscitation in IL-10 KO as compared to C57/BL6 mice; however this did not reach statistical significance. Serum MCP-1 levels were significantly increased in IL-10 KO mice 3 and 24 h following resuscitation as compared to C57/BL6 mice. In IL-10 KO mice, pulmonary MPO activity was significantly increased 3 h following resuscitation and after 24 h histological signs of acute lung injury were more apparent than in C57/BL6 mice. In contrast, no significant differences in any liver parameters were detected between IL-10 KO and C57/BL6 mice. Our data indicate that an endogenous IL-10 deficiency augments acute lung but not liver injury following hemorrhagic shock.
在失血性休克和创伤中，患者容易发生全身性炎症并伴有远隔器官功能障碍，这被认为是由促炎介质引起的。本研究调查免疫调节细胞因子白细胞介素-10（IL-10）在失血性休克后器官功能障碍发生过程中的作用。将雄性C57/BL6小鼠和IL-10基因敲除（KO）小鼠进行容量控制性失血性休克3小时，随后进行复苏。复苏后3小时或24小时处死动物。为评估全身性炎症，使用Luminex多重检测平台测量血清白细胞介素-6（IL-6）、IL-10、KC和单核细胞趋化蛋白-1（MCP-1）浓度；通过肺髓过氧化物酶（MPO）活性和肺组织学评估急性肺损伤（ALI），通过肝MPO活性、肝IL-6水平和血清谷丙转氨酶（ALT）水平评估急性肝损伤。与C57/BL6小鼠相比，IL-10 KO小鼠复苏后3小时血清IL-6和KC水平有升高趋势，但未达到统计学显著性。与C57/BL6小鼠相比，IL-10 KO小鼠复苏后3小时和24小时血清MCP-1水平显著升高。在IL-10 KO小鼠中，复苏后3小时肺MPO活性显著升高，24小时后急性肺损伤的组织学征象比C57/BL6小鼠更明显。相比之下，IL-10 KO小鼠和C57/BL6小鼠之间在任何肝脏参数方面均未检测到显著差异。我们的数据表明，内源性IL-10缺乏会加重失血性休克后的急性肺损伤，但不会加重肝损伤。
