When host defense goes awry: Modeling sepsis-induced immunosuppression

Abstract

Sepsis is associated with an initial hyperinflammatory state; however, therapeutic trials targeting the inflammatory response have yielded disappointing results. It is now appreciated that septic patients often undergo a period of relative immunosuppression, rendering them susceptible to secondary infections. Interest in this phenomenon has led to the development of animal models to study the immune dysfunction of sepsis. In this review, we analyze the available models of sepsis-induced immunosuppression.

Figure 1

Evolution of sepsis. A state of relative immune paralysis often develops concurrently or subsequent to the initial inflammatory state of sepsis, resulting in increased susceptibility to secondary infections. Although most patients survive the initial insult of sepsis, they can succumb to a secondary infection if the balance between pro- and anti-inflammatory immune responses is dysregulated.