Reversibility of Immune Dysfunction Following Pediatric Thermal Injury

Pediatric thermal injury induces immune dysfunction, which is associated with adverse clinical outcomes (eg, nosocomial infections [NIs]). As such, it is crucial to identify those most at risk for developing NI and determine immunomodulating therapeutics to augment the immune response. Our hypothesis was that immune suppression after pediatric thermal injury is reversible ex-vivo using the immunomodulators recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) and varlilumab (CD27-agonist). We enrolled 141 pediatric patients with acute thermal injuries from a single burn center. Blood samples were taken within the first week after injury to analyze immune function and ex-vivo reversibility. Pediatric patients with burn injuries who went on to develop an NI displayed a decrease in innate (ex-vivo lipopolysaccharide [LPS]-induced tumor necrosis factor alpha [TNFα] production capacity) and adaptive immune function (ex-vivo phytohemagglutinin [PHA]-induced interleukin [IL]-10 production capacity) compared to patients with burn injuries who recovered without infection. After correcting immune function measurements by the total number of cells, the ratio of LPS-induced TNFα/CD14+ monocytes decreased within the first 72 h for patients with burn injuries who developed an NI, whereas PHA-induced IL-10/CD4+ lymphocytes was significantly decreased at days 4-7. Samples co-incubated with GM-CSF significantly increased ex-vivo LPS-induced TNFα, while samples containing CD27 increased PHA-induced IL-10 production capacity, in the first 72 h, compared to samples that did not receive immunomodulators. The results of our study identified key markers to discover who is most at risk for developing NI, and provided early evidence of immunomodulators that may enhance immune function early after pediatric burn injury.