Trends in Microbiology
ReviewCecal ligation and puncture: the gold standard model for polymicrobial sepsis?
Section snippets
Sepsis therapies: search for a needle in a haystack
Tight regulation of the immune system is essential for maintaining the balance between protective and tissue-damaging inflammatory responses. Therefore, local inflammatory responses are finely regulated and cease when the causative factor is removed. However, if the inflammatory reaction becomes dysregulated, systemic activation of the innate immune system becomes excessive and results in systemic inflammatory response syndrome (SIRS) or sepsis [1].
SIRS and sepsis are systemic reactions to
The upsides and downsides of animal models of sepsis: is CLP the gold standard?
Although sepsis is one of the most difficult clinical conditions to model in animals, different animal models have been developed. These commonly follow one of three strategies: (i) administration of exogenous toxins, such as zymosan and lipopolysaccharadide (LPS); (ii) administration of viable pathogens, such as bacteria and viruses; and (iii) alteration of the endogenous protective barrier of the animal. The CLP model and the colon ascendens stent peritonitis (CASP) model are examples of
The CLP model is important for sepsis research
Animal models are an indispensable tool for understanding the molecular and genetic mechanisms of sepsis. The availability of a variety of mutant mouse strains allows the study of the role of specific genes and has greatly contributed to our knowledge of the immune responses associated with experimental sepsis. Here, we summarize the findings obtained by targeting specific components of the immune system in CLP-induced sepsis.
Strategies to bridge the gap between bench and bedside
Although the CLP model has greatly contributed to our understanding of the pathophysiological and immunological features of clinical sepsis, it does not reproduce the whole spectrum of human sepsis. Many promising therapeutic agents that were effective in animal studies, including high-dose GCs [34], LPS-targeting agents 35, 36, and selective blockers of inflammatory mediators, all failed to demonstrate a similar benefit in human clinical trials [33]; very few therapies have been translated to
Concluding remarks and future perspectives
Sepsis is a major problem with high incidence and mortality rates. Appropriate animal models are crucial for studying sepsis, although most such models are not directly relevant for investigations of the pathophysiology of human sepsis. Nevertheless, the CLP model is one of the best representations of human sepsis and has made important contributions to our knowledge of the inflammatory components involved in sepsis and to the identification of therapeutic targets. The CLP model has been
Acknowledgments
The authors wish to acknowledge Dr. Amin Bredan for critical review of the manuscript. Research in the authors’ laboratory is sponsored by the Fund for Scientific Research-Flanders, the Interuniversity Attraction Poles Program of the Belgian Science Policy (IAP VI/18), the Belgische Vereniging tegen Kanker, and the VIB.
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