Non-Surgical Model of Sepsis and Inflammation2018-11-29T10:16:04+00:00
THE SMART SOLUTION FOR
PRECLINICAL DEVELOPMENT

NON-SURGICAL MODEL OF SEPSIS AND INFLAMMATION

SERVICE DESCRIPTION

In this model, a cecal slurry is used to induce septic peritonitis resulting in systemic bacteremia, organ infection and eventual systemic release of cytokines.  The model is highly reproducible, easy to monitor by a variety of endpoints, and closely mimics clinical sepsis.  By titrating the amount of cecal slurry used, the severity of the septic response can be adjusted to the needs of the experimenter.

APPLICATIONS

  • The model is a robust and reproducible preclinical model of poly-microbial sepsis to facilitate drug screening. It can be used in a variety of different types of studies including development of antibiotics, antithrombotics, immune modifiers, and diagnostics.

Sepsis Graph

 Groups of 8 mice each received intraperitoneal (IP) injections at doses ranging from 0.5 gm/kg to 4 gm/kg.
Animals were monitored every hour and deaths recorded.  Survival was dose dependent.
  • Because infection is poly-microbial, involving both gram negative and gram positive bacteria, a wide range of pattern recognition receptors such as Toll-Like Receptors are activated on a variety of immune cells, mimicking sepsis.
  • The model is useful for diagnostic and therapeutic studies of sepsis induced by pathogens, sterile sepsis or by trauma as the inflammatory response and Multi-Organ Dysfunction Syndrome (MODS) characteristic of Systemic Inflammatory Response Syndrome (SIRS) is similar whether induced by inflammation or by trauma.
 

METHODOLOGY

Mice are euthanized and their ceca removed.  Cecal contents are extracted, diluted with cold 5% dextrose and passed through an 18-gauge needle to break up solids, and stored in aliquots at -80oC.

For injection, the cecal slurry is thawed rapidly at 37oC and then equilibrated to room temperature.   Groups of mice receive intraperitoneal (IP) injections at doses ranging from 0.5 gm/kg to 4 gm/kg. Animals are monitored and deaths recorded. 

If preferred, the model can be run using a modified Schwartzman reaction where a priming dose of lipo­poly­saccharide is given to the mice to sensitize them prior to administration of the cecal slurry.

OPTIONS

  • Drug Administration Route:  Intravenous, Intramuscular, Continuous Infusion

  • Reference Substance & Control:Vancomycin  (or other reference antibiotic); vehicle

  • Length/Endpoint: Three to Four Days Post Infection

  • Assays & Measurements: Survival, Bacterial Counts, Cytokines, Chemokines, Blood Cell Counts
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Proven Expertise

We have experience with a variety of mammalian species used for vaccine and drug development. Our studies range from single digit to hundreds of animals.

Our scientists, with over 15 years of GLP experience, provide all aspects of the GLP process from design to regulatory support of your IND, IDE or PMA FDA submission.

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