The disconnect between animal models of sepsis and human sepsis

Abstract

Frequently used experimental models of sepsis include cecal ligation and puncture, ascending colon stent peritonitis, and the i.p. or i.v. injection of bacteria or bacterial products (such as LPS). Many of these models mimic the pathophysiology of human sepsis. However, identification of mediators in animals, the blockade of which has been protective, has not translated into clinical efficacy in septic humans. We describe the shortcomings of the animal models and reasons why effective therapy for human sepsis cannot be derived readily from promising findings in animal sepsis.

Dysfunctional expansion of hematopoietic stem cells and block of myeloid differentiation in lethal sepsis

“…23 Thus, it is very important that the results are viewed in the context of the in vivo model of infection used. 7,8,24 There is evidence that the mechanisms regulating neutrophil production and migration may change considerably with the severity of sepsis within the same experimental model.…”

Antioxidant and Anti-inflammatory Effects of Curcumin Against Hepatorenal Oxidative Injury in the Experimental Sepsis Model Created in Rats

“…The CLP model used in the present study creates a model similar to the clinical features of septic shock and resembles human sepsis, as the CLP model displays hypodynamic and hypometabolic phases following the hypermetabolic phase. [20] Therefore, it is the closest model to the clinical situation among sepsis models in rats. Unlike the other models (models created by injection of lipopolysaccharides or by intravenous or intraperitoneal infusion of live bacteria), the CLP model has advantages such as providing continuous intraperitoneal contamination without impairing the intestinal integrity, leading to a representation of septic shock in which numerous types of microorganisms are observed (polymicrobial), thus creating a model similar to clinical septic shock (perforated appendicitis, diverticulitis, and colon perforation).…”

Candidate inhibitors of porcine complement

“…A systemic inflammatory response may occur with the compartmentilazed infection as source, but the limited observation time of study IV probably prevented that. IP challenge was therefore not conducted in study V. CLP might be the model that best mimic clinical sepsis (178,179), and is frequently used in small animals. Peritonitis induced sepsis models are also conducted in pigs (167), and although CLP is possible to conduct and has been described in pig models (180), it is rarely used.…”