Early adaptive immune suppression in children with septic shock: a prospective observational study

Introduction: Innate immune suppression occurs commonly in pediatric critical illness, in which it is associated with adverse outcomes. Less is known about the adaptive immune response in critically ill children with sepsis. We designed a single-center prospective, observational study to test the hypothesis that children with septic shock would have decreased adaptive immune function compared with healthy children and that among children with sepsis, lower adaptive immune function would be associated with the development of persistent infection or new nosocomial infection. Methods: Children (18 years or younger) 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 with ex vivo phytohemagglutinin (PHA)-induced cytokine production capacity of isolated CD4(+) T cells. Percentage of regulatory T cells was measured with flow cytometry. Absolute lymphocyte counts were recorded when available. Results: In total; 22 children with septic shock and eight healthy controls were enrolled. Compared with those from healthy children, CD4+ T cells isolated from septic shock children on Days 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 antiinflammatory cytokines interleukin (IL)-4 (P = 0.03) and IL-10 (P = 0.02). Among septic shock 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 with septic shock children who did not. Percentage of regulatory T cells (CD4(+)-CD25(+)CD127(10)) did not differ among groups. Conclusions: Adaptive immune suppression may occur early in the course of pediatric septic shock and is associated with adverse infection-related outcomes.