TITLE:
Anti-Inflammatory Pre-Treatment to Reduce Mobilization-Induced Liver Inflammation in Mice: Novel Model to Study Liver Injury
AUTHORS:
T. Hendrikx, C. Piersma, D. K. Dhar, L. Mpabanzi, J. J. W. Schreurs, M. Malagó, R. Shiri-Sverdlov, S. W. M. Olde Damink
KEYWORDS:
Liver Surgery, Hepatocellular Damage, Inflammation, Translational Model, Post-Resectional Liver Failure
JOURNAL NAME:
Modern Research in Inflammation,
Vol.4 No.1,
May
25,
2015
ABSTRACT: 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.