Journal Article

Comprehensive comparison of three different animal models for systemic inflammation

Lupp, Amelie, Zohles, Franziska, Seemann, Semjon

2017

Overview

Background To 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. Methods Systemic 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. Results Treating 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. Conclusions The 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Animal models / Animals / Apoptosis / Biomedical and Life Sciences / Biomedicine / Biotransformation / Blood / Blood circulation / Blood Glucose - analysis / Care and treatment / Cecum / Cecum - immunology / Cecum - surgery / Cell adhesion & migration / CLP / Contamination / Cytokines / Cytokines - blood / Diagnosis / Disease Models, Animal / Glucose / Hepatocytes / Immune system / Immunohistochemistry / Inflammation / Inflammation - etiology / Inflammation - physiopathology / Laboratory animals / Ligation - adverse effects / Lipopolysaccharides / Lipopolysaccharides - pharmacology / Liver / Liver - metabolism / LPS / Male / Mice / Mice, Inbred C57BL / Mortality / Organ Specificity / Organs / Oxidative Stress / PCI / Peritoneal Diseases - immunology / Peritoneum / Physiological aspects / Rodents / Sepsis / Spleen / Studies / Systemic inflammation / Time Factors