Experimental models of Gram-negative sepsis

Background: The mortality rate from sepsis has improved little over the pas t two decades. One reason for this has been the use of flawed or inappropri ate experimental models in preclinical sepsis studies. Methods: A literature review of animal models of sepsis was performed follo wing a Medline search based on the following medical subject headings: dise ase models, endotoxin, inflammation, peritonitis and sepsis. Additional ref erences were identified from the papers identified in the search. Results and conclusion: Many animal models of sepsis have been described bu t none has proved to be superior. Extrapolation of results from endotoxicos is or bacterial infusion models should be regarded with caution. Peritoniti s models should be accepted as the 'gold standard' but the use of appropria te virulent bacterial species needs to be ensured. A standardized panel of animal models for the preclinical assessment of immunomodulatory agents sho uld be established, including at least one immunosuppressed model to simula te the immunocompromised patient with sepsis. A uniform and valid definitio n of sepsis applicable to both small and large animal species is required.