Reversibility of Immune Dysfunction Following Pediatric Thermal Injury

Abstract Pediatric thermal injury induces immune dysfunction, which is associated with adverse clinical outcomes (e.g., nosocomial infections NI). 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 immune suppression after pediatric thermal injury is reversible ex-vivo using immunomodulators recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) and varlilumab (CD27-agonist). We enrolled 141 pediatric burn patients from a single, pediatric burn center with acute thermal injury. Blood samples were taken within the first week after injury to analyze immune function and ex-vivo reversibility. Pediatric burn patients who went on to develop a 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 burn patients who recovered without infection. By correcting immune function measurements by the total number of cells, the ratio of LPS-induced TNFα/CD14+ monocytes, in the first 72 h, was decreased for burn patients who developed a 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 those most at risk for development of NI and provided early evidence of immunomodulators that may enhance immune function early after pediatric burn injury.