Why do animal models (sometimes) fail to mimic human sepsis?
Departments of Pathology and Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. OBJECTIVE: To describe potential mechanisms that may account for the observation that drugs that work in treating sepsis in animal models often fail in sepsis trials in patients. DATA SOURCE: MEDLINE searches were used to provide the key information. DATA SUMMARY: Most animal studies are performed acutely in young healthy animals, whereas a significant percentage of the clinical population is elderly with many secondary complications (e.g., diabetes, systemic vascular disease, high blood pressure, immune suppression, cancer). Furthermore, unlike the acute challenge presented in most animal studies, many of the septic patients’ clinical histories indicate a relatively slow onset of the disease. In many animal studies, intervention occurs before or during the very early stages of sepsis, when inflammatory cytokine levels are still rising and both organ d
