Early adaptive immune suppression in children with septic shock: a prospective observational study
Critical Care 2014, 18:R145 doi:10.1186/cc13980Published: 8 July 2014
Innate immune suppression occurs commonly in pediatric critical illness, where it is associated with adverse outcomes. Less is known about the adaptive immune response in critically ill septic children. We designed a single-center prospective, observational study to test the hypothesis that children with septic shock would have decreased adaptive immune function compared to healthy children and that among septic children, lower adaptive immune function would be associated with the development of persistent infection or new nosocomial infection.
Children (<18 years of age) who were admitted to the pediatric intensive care unit with septic shock (by International Consensus Criteria) were enrolled in the study. Blood samples were taken within 48 hours of sepsis onset and again on Day 7 of illness. Adaptive immune function was assessed by ex-vivo phytohemagglutinin (PHA)-induced cytokine production capacity of isolated CD4+ T cells. Percentage of regulatory T cells was measured by flow cytometry. Absolute lymphocyte counts were recorded when available.
A total of 22 septic children and 8 healthy controls were enrolled. Compared to healthy children, CD4+ T cells isolated from septic children on Day 1 to 2 of illness and stimulated with PHA produced less of the pro-inflammatory cytokine interferon gamma (IFN-gamma) (P = 0.002), and the anti-inflammatory cytokines interleukin (IL)-4 (P = 0.03) and IL-10 (P = 0.02). Among septic children, those who went on to develop persistent or nosocomial infection had decreased T cell ex-vivo PHA-induced production of IFN- gamma (P = 0.01), IL-2 (P = 0.01), IL-4 (P = 0.008), and IL-10 (P = 0.001) compared to septic children who did not. Percent of regulatory T cells (CD4+CD25+CD127lo) did not differ among groups.
Adaptive immune suppression may occur early in the course of pediatric septic shock and is associated with adverse infection-related outcomes.