Sepsis Model
Sepsis Model
Utilizing clinical-grade polymicrobial infection and endotoxemia protocols, our platform captures systemic inflammatory response syndrome (SIRS), cytokine storm cascades, multi-organ dysfunction syndrome (MODS), and septic shock.
Indications & Applications
- Efficacy Screening for Anti-Sepsis Therapeutics: In vivo evaluation of novel small molecules, biologicals, targeted monoclonal antibodies, and engineered cell therapies for severe sepsis and septic shock.
- Anti-Cytokine Storm & Immunomodulatory Drugs: Validation of candidates targeting hyper-inflammatory cytokine release (e.g., TNF-α, IL-6, IL-1β inhibitors) and immune checkpoint regulators.
- Endotoxin Neutralizers & TLR Pathway Inhibitors: Screening agents designed to bind/neutralize lipopolysaccharide (LPS) or block downstream TLR4/NF-κB signaling pathways.
- Multi-Organ Failure Protection (MODS): Assessment of therapeutics aimed at mitigating acute lung injury (ALI/ARDS), acute kidney injury (AKI), cardiac dysfunction, and vascular leakage.
- Adjuvant & Fluid Resuscitation Therapy Testing: Evaluation of combination regimens pairing novel immunomodulators with standard-of-care antimicrobial or resuscitation protocols.
Modeling Methodologies
1. Cecal Ligation and Puncture (CLP) Model
Recognized as the gold standard in preclinical sepsis research. Surgical ligation and controlled needle puncture of the cecum induce polymicrobial peritonitis and bacteremia, reproducing the clinical dynamics of systemic infection, acute inflammation, and multi-organ damage.
2. Lipopolysaccharide (LPS)-Induced Endotoxemia Model
Systemic administration of bacterial endotoxin (LPS) triggers rapid activation of pattern recognition receptors (TLR4), producing a highly reproducible cytokine storm, systemic hypothermia/fever, hypotension, and acute septic shock for fast-turnaround screening.
3. Fecal Peritonitis / Live Pathogen Inoculation Model
Intraperitoneal injection of cecal slurry or defined bacterial pathogens (e.g., Escherichia coli) provides a titratable, reproducible model of acute peritoneal sepsis ideal for evaluating antimicrobial efficacy alongside host-directed therapies.
Clinical Relevance & Translation
- Pathophysiological Homology: Accurately mimics human septic shock features including hyper/hypo-inflammatory biphasic responses, endothelial dysfunction, and organ failure.
- Translational Biomarkers: Evaluates clinical plasma biomarkers (procalcitonin, lactate, pro-inflammatory cytokines) aligned with ICU monitoring standards.
- Adjustable Severity: Puncture gauge, ligation length, or toxin dosage can be calibrated to model moderate sepsis or lethal septic shock for precise survival analysis.
Key Evaluation Endpoints
| Endpoint Domain | Specific Parameters & Assays | Pathological Significance |
|---|---|---|
| Systemic & Survival Dynamics | • Survival Rate & Kaplan-Meier Curves • Murine Sepsis Score (MSS) & Hypothermia • Mean Arterial Pressure (MAP) & Heart Rate |
Determines overall therapeutic survival benefit, disease severity, and hemodynamic shock status. |
| Systemic Inflammation & Cytokine Storm | • Serum TNF-α, IL-6, IL-1β, IL-10, HMGB1 • Plasma Procalcitonin (PCT) & CRP • Circulating Endotoxin (LPS) Levels |
Quantifies active hyper-inflammatory cytokine storm cascades and systemic bacterial dissemination. |
| Multi-Organ Function & Biochemistry | • Kidney: Serum Creatinine, BUN, NGAL • Liver: ALT, AST, Total Bilirubin • Metabolic: Blood Lactate & Arterial pH |
Assesses acute kidney injury (AKI), acute hepatic dysfunction, hypoperfusion, and metabolic acidosis. |
| Histopathology & Vascular Leakage | • Lung/Kidney/Liver H&E (Neutrophil Infiltration) • Evans Blue Dye Permeability Assay • Tissue Myeloperoxidase (MPO) Activity |
Evaluates microvascular leak, tissue edema, pulmonary neutrophil sequestration, and parenchymal damage. |
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