Tom van der Poll1. 1. Center of Infection and Immunity Amsterdam, Center of Experimental and Molecular Medicine, and Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. t.vanderpoll@amc.uva.nl
Abstract
BACKGROUND: A variety of sepsis models have been used to unravel pathophysiologic processes and to examine the effects of novel therapeutic interventions. The lack of therapeutic efficacy of numerous compounds in clinical sepsis trials, despite glorious results in animal models of sepsis, has raised doubt and debate about the usefulness of such models. METHODS: Review of the pertinent literature. RESULTS: Many sepsis models have been described, none of which is ideal. Clinical sepsis can originate from different sources, can be accompanied by many complicating conditions, and strikes human beings with strongly variable genetic backgrounds, co-morbidities, and drug usages. To provide answers to the three main objectives of research-insight into the regulation of normal host defense mechanisms in the early stages of infection; the mechanisms underlying dysregulation of the host response; and proof of principle for the mechanism of action of novel therapeutic agents and to establish their efficacy and potential harm-diverse models are required. The future of sepsis research lies in the systematic combination of models, together with in vitro studies and carefully designed and monitored Phase I/II clinical studies. CONCLUSION: This review discusses the nature of various animal sepsis models and the way their results should be interpreted.
BACKGROUND: A variety of sepsis models have been used to unravel pathophysiologic processes and to examine the effects of novel therapeutic interventions. The lack of therapeutic efficacy of numerous compounds in clinical sepsis trials, despite glorious results in animal models of sepsis, has raised doubt and debate about the usefulness of such models. METHODS: Review of the pertinent literature. RESULTS: Many sepsis models have been described, none of which is ideal. Clinical sepsis can originate from different sources, can be accompanied by many complicating conditions, and strikes human beings with strongly variable genetic backgrounds, co-morbidities, and drug usages. To provide answers to the three main objectives of research-insight into the regulation of normal host defense mechanisms in the early stages of infection; the mechanisms underlying dysregulation of the host response; and proof of principle for the mechanism of action of novel therapeutic agents and to establish their efficacy and potential harm-diverse models are required. The future of sepsis research lies in the systematic combination of models, together with in vitro studies and carefully designed and monitored Phase I/II clinical studies. CONCLUSION: This review discusses the nature of various animal sepsis models and the way their results should be interpreted.
Authors: Alexandre Kanashiro; Fabiane Sônego; Raphael G Ferreira; Fernanda V S Castanheira; Caio A Leite; Vanessa F Borges; Daniele C Nascimento; David F Cólon; José Carlos Alves-Filho; Luis Ulloa; Fernando Q Cunha Journal: Pharmacol Res Date: 2016-12-12 Impact factor: 7.658