Animal models of sepsis

Area of Science:

• Sepsis Pathophysiology
• Animal Modeling
• Translational Research

Background:

• Sepsis knowledge is rapidly advancing, driven by evolving pathogenetic concepts and therapeutic strategies.
• Animal models are essential for this progress, though they involve compromises between realism and simplification.
• Current models require analysis for their validity and clinical relevance.

Purpose of the Study:

• To analyze the validity and clinical relevance of different animal models of sepsis.
• To compare models with and without infectious foci against current pathogenetic understanding.
• To guide the selection of optimal sepsis models for research.

Main Methods:

• Review and analysis of existing literature on animal models of sepsis.
• Categorization of models into those without infectious foci (endotoxemia, bacteremia) and those with infectious foci (peritonitis, fecal inoculation, bowel perforation).
• Evaluation of models based on their ability to reproduce sepsis characteristics, immune reactions, and clinical scenarios.

Main Results:

• Models without infectious foci are controlled and standardized but lack a protracted immune response and infectious focus.
• Models with infectious foci (fecal peritonitis, bowel perforation) better reproduce the full spectrum of pathogens and pathophysiologic/immunologic features of clinical sepsis.
• Models with infectious foci show poor interlaboratory standardization due to challenges in controlling bacterial load.

Conclusions:

• Choosing appropriate sepsis models, particularly those with infectious foci, is crucial for clinical relevance.
• Incorporating clinical therapies (resuscitation, antibiotics, surgery) and comorbidities into models is indispensable for optimizing them.
• Further refinement of animal models is needed to better bridge the gap between experimental findings and clinical practice in sepsis management.