Comprehensive comparison of three different animal models for systemic inflammation

Journal of Biomedical Science

Research

Franziska Zohles¹  Semjon Seemann¹  Amelie Lupp¹ 

[1] Institute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Str. 1, 07747, Jena, Germany;

关键词: LPS;    PCI;    CLP;    Systemic inflammation;    Oxidative stress;    Cytokines;   

DOI  :  10.1186/s12929-017-0370-8

 received in 2017-06-27, accepted in 2017-08-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundTo mimic systemic inflammation in humans, different animal models have been developed. Since these models are still discussed controversially, we aimed to comparatively evaluate the most widely used models with respect to the systemic effects, the influence on organ functions and to the underlying pathophysiological processes.MethodsSystemic inflammation was induced in C57BL/6N mice with lipopolysaccharide (LPS) treatment, peritoneal contamination and infection (PCI), or cecal ligation and puncture (CLP). Blood glucose and circulating cytokine levels were evaluated at 0, 2, 4, 6, 12, 24, 48, and 72 h after induction of inflammation. Additionally, oxidative stress in various organs and liver biotransformation capacity were determined. Markers for oxidative stress, apoptosis, infiltrating immune cells, as well as cytokine expression patterns, were assessed in liver and spleen tissue by immunohistochemistry.ResultsTreating mice with LPS and PCI induced a very similar course of inflammation; however, LPS treatment elicited a stronger response. In both models, serum pro-inflammatory cytokine levels rapidly increased whereas blood glucose decreased. Organs showed early signs of oxidative stress, and apoptosis was increased in splenic cells. In addition, liver biotransformation capacity was reduced and there was pronounced immune cell infiltration in both the liver and spleen. Mice exposed to either LPS or PCI recovered after 72 h. In contrast, CLP treatment induced comparatively fewer effects, but a more protracted course of inflammation.ConclusionsThe LPS model of systemic inflammation revealed to be most suitable when being interested in the impact of new therapies for acute inflammation. When using the CLP model to mimic human sepsis more closely, a longer time course should be employed, as the treatment induces delayed development of systemic inflammation.

【 授权许可】

CC BY   
© The Author(s). 2017