Immunodesign of experimental sepsis by cecal ligation and puncture
Open accessAbstract
Sepsis remains a prevalent clinical challenge and the underlying pathophysiology is still poorly understood. To investigate the complex molecular mechanisms of sepsis, various animal models have been developed, the most frequently used being the cecal ligation and puncture (CLP) model in rodents. In this model, sepsis originates from a polymicrobial infectious focus within the abdominal cavity, followed by bacterial translocation into the blood compartment, which then triggers a systemic inflammatory response. A requirement of this model is that it is performed with high consistency to obtain reproducible results. Evidence is now emerging that the accompanying inflammatory response varies with the severity grade of sepsis, which is highly dependent on the extent of cecal ligation. In this protocol, we define standardized procedures for inducing sepsis in mice and rats by applying defined severity grades of sepsis through modulation of the position of cecal ligation. The CLP procedure can be performed in as little as 10 min for each animal by an experienced user, with additional time required for subsequent postoperative care and data collection.
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The CLP model has been widely used for decades as the gold standard sepsis model because it establishes hemodynamics, metabolic changes, and inflammatory progression similar to those observed in human sepsis.
“In our current study, we established an SAE model via cecal ligation and puncture (CLP) surgery, which has been widely used for decades as the gold standard sepsis model because it establishes hemodynamics, metabolic changes, and inflammatory progression similar to those observed in human sepsis (Rittirsch et al., 2009).”
From The modulatory effects of gut microbes and metabolites on blood-brain barrier integrity and brain function in sepsis-associated encephalopathy (2023) · cites this paper as Rittirsch et al., 2009
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- Authors
- Rittirsch, D., Huber-Lang, M. S., Flierl, M. A., & Ward, P. A.
- Affiliations
- University of Michigan (US)
- University Hospital Ulm (DE)
- Corresponding author
- Ward, Peter A
- Venue
- Nature Protocols
- Published
- 2008-12-11
- Volume
- 4
- Issue
- 1
- Pages
- 31-36
- ISSN
- 1750-2799 (ISSN-L)
- 1754-2189
- PMC
- PMC2754226
- OpenAlex
- W2023945291
- Cited by
- 2,209
- References
- 19
- Citations by year
- 2026: 190 · 2025: 194 · 2024: 216 · 2023: 212 · 2022: 198 · 2021: 183 · 2020: 161 · 2019: 113 · 2018: 107 · 2017: 113 · 2016: 103 · 2015: 113 · 2014: 104 · 2013: 66 · 2012: 54
- FWCI
- 20.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Protocols (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- National Institutes of Health (2r01gm061656-09, 5r01gm029507-30)
- National Heart, Lung, and Blood Institute (HL 31963, P01HL031963)
- National Institute of General Medical Sciences (R01-GM061656, GM‐61656, R37GM029507, GM 029507, R01-GM029507)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- sepsis, cecal ligation and puncture, animal models of sepsis, bacterial translocation, systemic inflammatory response, co-infection, mouse and rat models
- MeSH terms
- Animals, Cecum, Disease Models, Animal, Ligation, Sepsis, Mice, Rats
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