New approaches to the study of sepsis

Abstract

Models of sepsis have been instructive in understanding the sequence of events in animals and, to an extent, in humans with sepsis. Events developing early in sepsis suggest that a hyperinflammatory state exists, accompanied by a buildup of oxidants in tissues reflective of a redox imbalance. Development of immunosuppression and degraded innate and adaptive immune responses are well-established complications of sepsis. In addition, there is robust activation of the complement system, which contributes to the harmful effects of sepsis. These events appear to be associated with development of multiorgan failure. The relevance of animal models of sepsis to human sepsis and the failure of human clinical trials are discussed, together with suggestions as to how clinical trial design might be improved. Currently there is no FDA-approved drug for use in sepsis. This Review discusses the relevance of animal models to human sepsis and the failure of human clinical trials and provides suggestions as to how clinical trial design might be improved. © 2012 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.