Immune modulation in sepsis

Abstract

The vast majority of morbidity and mortality from sepsis can be attributed to the host immune response to infection rather than the infection itself. The innate and adaptive immune systems both contribute to this process. Numerous therapies aimed at reducing the pro-inflammatory burden of acute sepsis have been studied in clinical trials, with most producing disappointing results. The inflammatory response to sepsis has since been shown to be highly dynamic, with a period of compensatory down- regulation of the pro-inflammatory response dominating in the subacute phase of illness. This state, when prolonged and severe, is termed immunoparalysis and is associated with increased risks for nosocomial infection and death. Early evidence suggests that this state may be reversible with beneficial effects on outcomes. Other strategies for manipulating the inflammatory response in the setting of sepsis include the use of corticosteroids, immunonutrition, extracorporeal therapies, intravenous immunoglobulin, and the modulation of pre-existing immunosuppressive drugs. Clinical trials investigating immune modulation in sepsis have largely been done without the benefit of prospective immune monitoring and have rarely been done in children. Immune phenotype-directed therapies aimed at restoring immunologic homeostasis in pediatric sepsis represent the next step on the path toward improving sepsis outcomes in children.