Different Preclinical Animal Models for Sepsis

Abstract

Sepsis is a significant cause of illness and death, primarily due to the multiple organ dysfunction it can induce. Despite promising results in preclinical studies, most clinical trials testing new treatment strategies for sepsis have failed to show effectiveness. One possible reason for this discrepancy is the misinterpretation of preclinical data, particularly when using animal models that do not adequately mimic human sepsis. This review discusses the potential and limitations of various animal models used in sepsis research, aiming to determine the extent to which these findings are applicable to human sepsis. These animal models encompass different methods such as intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia, and meningitis models. Animal models are crucial in developing new sepsis therapies because they provide essential information about pharmacokinetics, toxicity, and the mechanisms of drug action that cannot be obtained through other means. They offer insights into drugs and initial treatments interact with the body, assess the safety and efficacy of drugs, and investigate the underlying mechanisms of sepsis. However, it is important to acknowledge the limitations of animal models. Animals used in research may not fully replicate the complexity and heterogeneity of human sepsis, leading to differences in treatment response. Ethical considerations also restrict certain invasive procedures in human subjects that can be performed in animal models. These factors contribute to challenges in translating preclinical findings into successful clinical trials.