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

T. Hendrikx; C. Piersma; D. K. Dhar; L. Mpabanzi; J. J. W. Schreurs; M. Malagó; R. Shiri-Sverdlov; S. W. M. Olde Damink

doi:10.4236/mri.2015.41001

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Modern Research in Inflammation > Vol.4 No.1, May 2015

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

T. Hendrikx^1,2, C. Piersma³, D. K. Dhar^4,5, L. Mpabanzi^2,3, J. J. W. Schreurs^1,2, M. Malagó⁴, R. Shiri-Sverdlov^1,2, S. W. M. Olde Damink^2,3,4*

¹Department of Molecular Genetics, Maastricht University, Maastricht, The Netherlands.
²Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
³Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
⁴Department of HPB Surgery and Liver Transplantation, Royal Free Hospital, University College London, London, UK.
⁵Comparative Medicine Department, Organ Transplantation Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

DOI: 10.4236/mri.2015.41001 PDF HTML XML 4,676 Downloads 5,182 Views

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.

Keywords

Liver Surgery, Hepatocellular Damage, Inflammation, Translational Model, Post-Resectional Liver Failure

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Hendrikx, T. , Piersma, C. , Dhar, D. , Mpabanzi, L. , Schreurs, J. , Malagó, M. , Shiri-Sverdlov, R. and Damink, S. (2015) Anti-Inflammatory Pre-Treatment to Reduce Mobilization-Induced Liver Inflammation in Mice: Novel Model to Study Liver Injury. Modern Research in Inflammation, 4, 1-7. doi: 10.4236/mri.2015.41001.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Schemmer, P., Bradford, B.U., Bunzendahl, H., Lemasters, J.J. and Thurman, R.G. (2000) Gentle in Situ Liver Manipulation during Organ Harvest Increases Oxygen Consumption in Liver. Transplantation Proceedings, 32, 112. http://dx.doi.org/10.1016/S0041-1345(99)00902-1
[2]	Schemmer, P., Connor, H.D., Arteel, G.E., et al. (1999) Reperfusion Injury in livers Due to Gentle in Situ Organ Manipulation during Harvest Involves Hypoxia and Free Radicals. The Journal of Pharmacology and Experimental Therapeutics, 290, 235-240.
[3]	Schemmer, P., Schoonhoven, R., Swenberg, J.A., Bunzendahl, H. and Thurman, R.G. (1998) Gentle in Situ Liver Manipulation during Organ Harvest Decreases Survival after Rat Liver Transplantation: Role of Kupffer Cells. Transplantation, 65, 1015-1020. http://dx.doi.org/10.1097/00007890-199804270-00001
[4]	Van Den Broek, M.A., Shiri-Sverdlov, R., Schreurs, J.J., et al. (2013) Liver Manipulation during Liver Surgery in Humans is Associated with Hepatocellular Damage and Hepatic Inflammation. Liver International: Official Journal of the International Association for the Study of the Liver, 33, 633-641. http://dx.doi.org/10.1111/liv.12051
[5]	Van de Poll, M.C., Derikx, J.P., Buurman, W.A., et al. (2007) Liver Manipulation Causes Hepatocyte Injury and Precedes Systemic Inflammation in Patients Undergoing Liver Resection. World Journal of Surgery, 31, 2033-2038. http://dx.doi.org/10.1007/s00268-007-9182-4
[6]	Liaskou, E., Wilson, D.V. and Oo, Y.H. (2012) Innate Immune Cells in Liver Inflammation. Mediators of inflammation, 2012, Article ID: 949157. http://dx.doi.org/10.1155/2012/949157
[7]	Schemmer, P., Enomoto, N., Bradford, B.U., et al. (2001) Activated Kupffer Cells Cause a Hypermetabolic State after Gentle in Situ Manipulation of Liver in Rats. American Journal of Physiology Gastrointestinal and Liver Physiology, 280, G1076-G1082.
[8]	Ebert, E.C. (2009) Infliximab and the TNF-Alpha System. American Journal of Physiology Gastrointestinal and Liver Physiology, 296, G612-G620. http://dx.doi.org/10.1152/ajpgi.90576.2008
[9]	Hendrikx, T., Jeurissen, M.L., Bieghs, V., et al. (2015) Hematopoietic Overexpression of Cyp27a1 Reduces Hepatic Inflammation Independently of 27-Hydroxycholesterol Levels in Ldlr(-/-) Mice. Journal of Hepatology, 62, 430-436. http://dx.doi.org/10.1016/j.jhep.2014.09.027
[10]	(2012) An Inflammatory Assemblage. Nature Immunology, 13, 320. http://dx.doi.org/10.1038/ni.2268
[11]	Parekh, R. and Kaur, N. (2014) Liver Injury Secondary to Anti-TNF-Alpha Therapy in Inflammatory Bowel Disease: A Case Series and Review of the Literature. Case Reports in Gastrointestinal Medicine, 2014, Article ID: 956463. http://dx.doi.org/10.1155/2014/956463
[12]	Ebert, E.C., Das, K.M., Mehta, V. and Rezac, C. (2008) Non-Response to Infliximab May Be Due to Innate Neutralizing Anti-Tumour Necrosis Factor-Alpha Antibodies. Clinical and Experimental Immunology, 154, 325-31. http://dx.doi.org/10.1111/j.1365-2249.2008.03773.x
[13]	Rajamaki, K., Lappalainen, J., Oorni, K., et al. (2010) Cholesterol Crystals Activate the NLRP3 Inflammasome in Human Macrophages: A Novel Link between Cholesterol Metabolism and Inflammation. PloS One, 5, Article ID: e11765. http://dx.doi.org/10.1371/journal.pone.0011765
[14]	Samstad, E.O., Niyonzima, N., Nymo, S., et al. (2014) Cholesterol Crystals Induce Complement-Dependent Inflammasome Activation and Cytokine Release. Journal of Immunology, 192, 2837-2845. http://dx.doi.org/10.4049/jimmunol.1302484