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Animal and human models for sepsis.

Marc J Schultz1, Tom van der Poll

  • 1Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, G3-206, Meibergdreef 9, NL-1105 AZ Amsterdam, The Netherlands. m.j.schultz@amc.uva.nl

Annals of Medicine
|January 30, 2003
PubMed
Summary

Preclinical sepsis models have identified potential treatments, but clinical trials often fail. This review discusses model limitations and recommends using diverse models to improve sepsis therapy development.

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Area of Science:

  • * Sepsis research and preclinical modeling.
  • * Immunomodulatory drug development.
  • * Translational medicine challenges.

Background:

  • * Preclinical sepsis models have advanced understanding of disease pathophysiology and identified potential immunomodulatory treatments.
  • * Despite promising preclinical data, numerous clinical trials targeting sepsis have yielded disappointing outcomes.
  • * A significant gap exists between preclinical findings and clinical efficacy in sepsis treatment.

Purpose of the Study:

  • * To critically evaluate the advantages and disadvantages of various preclinical sepsis models.
  • * To investigate the impact of model choice on the efficacy of immunomodulatory strategies.
  • * To provide recommendations for optimizing preclinical testing of sepsis therapeutics.

Main Methods:

  • * Review and comparative analysis of existing preclinical sepsis models.
  • * Examination of studies comparing immunomodulatory agent efficacy in different model types.
  • * Discussion of the influence of infectious focus in sepsis models.

Main Results:

  • * Many commonly used sepsis models lack a relevant infectious focus, potentially skewing results.
  • * Immunomodulatory strategies show markedly different effects in models with versus without an infectious focus.
  • * The route of infection significantly impacts the observed outcomes in preclinical sepsis studies.

Conclusions:

  • * Preclinical sepsis models have limitations, particularly those lacking an infectious focus.
  • * Discrepancies in results between different model types hinder therapeutic translation.
  • * A combination of diverse preclinical models is recommended for evaluating new sepsis therapies before clinical trials.

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