Comprehensive comparison of three different animal models for systemic inflammation

Abstract

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.Electronic supplementary materialThe online version of this article (10.1186/s12929-017-0370-8) contains supplementary material, which is available to authorized users.

Circadian Rhythms Influence the Severity of Sepsis in Mice via a TLR2-Dependent, Leukocyte-Intrinsic Mechanism

“…LPS administration induced a high level of serum IL-6 at 2 h postinjection, which returned to background levels by 12 h (38). In contrast, CLP induced lower levels of serum IL-6 at 2 h postsurgery, but this cytokine remained elevated at 72 h (38). This is likely because during LPS endotoxemia, a large bolus of LPS is injected into the mouse and will be rapidly cleared from the body.…”

“…It is worth noting that the diurnal changes reported in the LPS model were substantial (34,35), whereas the diurnal changes we report in the CLP model are more subtle. A recent report directly compared the dynamics of the inflammatory cytokine response in the LPS versus CLP models (38). LPS administration induced a high level of serum IL-6 at 2 h postinjection, which returned to background levels by 12 h (38).…”

“…A recent report directly compared the dynamics of the inflammatory cytokine response in the LPS versus CLP models (38). LPS administration induced a high level of serum IL-6 at 2 h postinjection, which returned to background levels by 12 h (38). In contrast, CLP induced lower levels of serum IL-6 at 2 h postsurgery, but this cytokine remained elevated at 72 h (38).…”

Dietary Stevioside Supplementation Alleviates Lipopolysaccharide-Induced Intestinal Mucosal Damage through Anti-Inflammatory and Antioxidant Effects in Broiler Chickens

“…Lipopolysaccharide (LPS), an endotoxin secreted by APEC, is able to activate toll-like receptor 4 (TLR4). The activation of TLR4 triggers the phosphorylation of nuclear factor kappaB (NF-κB), and eventually promotes the synthesis of pro-inflammatory cytokines and induces oxidative stress [3][4][5]. The immune response of LPS administration is proven to be similar to avian pathogenic E. coli infection on the epithelial cell of chickens [6].…”

Efeito protetor do estradiol na disfunção da barreira epitelial intestinal induzida pela endotoxemia

“…Essas bactérias são compostas por duas membranas distintas, uma externa e outra interna, separadas entre si pelo periplasma. O LPS está localizado na face externa e induz um aumento da produção de mediadores pró-inflamatórios de forma robusta, intensa e rápida comparado a outros modelos experimentais, dentre eles, o modelo de ligadura e perfuração cecal e o de contaminação e infecção peritoneal (Seemann et al, 2017).…”