Early Immune Function and Duration of Organ Dysfunction in Critically Ill Children with Sepsis

Rationale: Late immune suppression is associated with nosocomial infection and mortality in adults and children with sepsis. Relationships between early immune suppression and outcomes in children with sepsis remain unclear. Objectives: Prospective observational study to test the hypothesis that early innate and adaptive immune suppression are associated with longer duration of organ dysfunction in children with severe sepsis or septic shock. Methods: Children younger than 18 years of age meeting consensus criteria for severe sepsis or septic shock were sampled within 48 hours of sepsis onset. Healthy control subjects were sampled once. Innate immune function was quantified by whole blood ex vivo LPS-induced TNF-alpha (tumor necrosis factor-alpha) production capacity. Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFN-gamma production capacity. Measurements and Main Results: One hundred two children with sepsis and 35 healthy children were enrolled. Compared with healthy children, children with sepsis demonstrated lower LPS-induced TNF-alpha production (P < 0.0001) and lower phytohemagglutinin-induced IFN-gamma production (P < 0.0001). Among children with sepsis, early innate and adaptive immune suppression were associated with greater number of days with multiple organ dysfunction syndrome and greater number of days with any organ dysfunction. On multivariable analyses, early innate immune suppression remained independently associated with increased multiple organ dysfunction syndrome days (adjusted relative risk, 1.2; 95% confidence interval, 1.03-1.5) and organ dysfunction days (adjusted relative risk, 1.2; 95% confidence interval, 1.1-1.3). Conclusions: Critically ill children with severe sepsis or septic shock demonstrate early innate and adaptive immune suppression. Early innate and adaptive immune suppression are associated with longer durations of organ dysfunction and may be useful markers to help guide future investigations of immunomodulatory therapies in children with sepsis.