Affiliations: Department of Pediatrics, The Ohio State University
College of Medicine, Section of Critical Care Medicine, Nationwide Children's
Hospital, The Research Institute at Nationwide Children's Hospital, Ohio,
USA
Note: [] Correspondence: Mark W. Hall, M.D., Critical Care Medicine,
Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.
Tel.: +1 614 722 3438; Fax: +1 614 722 3443; E-mail:
Mark.Hall@NationwideChildrens.org
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.
