Anti-Inflammatory Pre-Treatment to Reduce Mobilization-Induced Liver Inflammation in Mice: Novel Model to Study Liver Injury

摘要

Background: Liver surgery requires mobilization of the liver resulting in injury. Mobilization is the predominant cause of hepatocyte damage during liver surgery and jeopardizes post-operative liver function. Previously, mobilization-induced liver injury was found to be associated with inflammation. So far, anti-inflammatory drugs to potentially prevent liver inflammation following liver mobilization were not tested. In this study, we aimed to establish an in vivo mouse model of mobilization-induced liver injury and to evaluate the effect of anti-inflammatory pre-treatment before liver mobilization on liver inflammation. Methods: To develop a mouse model for mobilization-induced liver injury, C57BL/6 mice (n = 8) underwent surgery during which the liver was mobilized by gentle manipulation of the lobes with cotton-wool applicators for 15 minutes. In two control groups, the liver was left alone or was subjected to laparotomy only. An additional group was added that received anti-TNF treatment (Infliximab) 2 days prior to surgery. Liver samples were obtained 2 hours after mobilization and liver inflammation was analyzed by histology and inflammatory gene expression. Results: Gentle liver mobilization resulted in acute liver inflammation as indicated by increased recruitment of inflammatory cells and elevated inflammatory gene expression compared to controls. Infliximab pre-treatment had no effect on the inflammatory response in the liver. Conclusion: Our current model provides an excellent opportunity to study the effects of pre-treatment with anti-inflammatory drugs on mobilization-induced liver inflammation. Further studies are needed to investigate whether anti-inflammatory mediators can be used to prevent liver inflammation.