Abstract
IntroductionInnate 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.MethodsChildren (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.ResultsIn 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-γ) (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-γ (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+CD127lo) did not differ among groups.ConclusionsAdaptive immune suppression may occur early in the course of pediatric septic shock and is associated with adverse infection-related outcomes.
Highlights
Innate immune suppression occurs commonly in pediatric critical illness, in which it is associated with adverse outcomes
Adaptive immune suppression may occur in other critically ill pediatric populations, which we view as an important area of future study. This cohort of critically ill children with septic shock demonstrated early adaptive immune suppression compared with healthy children, with further suppression seen in children who went on to develop infectious complications
This was characterized by lower CD4+ T-cell cytokineproduction capacities and lymphopenia, but not by increased percentage of regulatory T cells
Summary
Innate immune suppression occurs commonly in pediatric critical illness, in which it is associated with adverse outcomes. Adult studies demonstrate alterations in CD4+ T cells in septic shock patients compared with nonseptic controls, including increased lymphocyte apoptosis; decreased proliferative capacity in response to antigen; skewing toward T cells that promote antiinflammatory cytokine responses (for example, TH2); and increased percentage of immunosuppressive regulatory T cells (Treg) [9,12,13,14,15]. These antiinflammatory T-cell phenotypes in adults are associated with increased risks of sepsis-related mortality [10,15]. Functional analyses of the adaptive immune response in septic shock children are lacking, and relationships between adaptive immune function and outcomes are unknown in this population
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