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Review
. 2019 Mar;8(1):42-50.
doi: 10.1055/s-0038-1676607. Epub 2019 Jan 2.

Immune Modulation in Pediatric Sepsis

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Free PMC article
Review

Immune Modulation in Pediatric Sepsis

Mark W Hall. J Pediatr Intensive Care. .
Free PMC article

Abstract

The initial host immune response to sepsis in children is characterized by a proinflammatory surge that can be associated with fever, capillary leak, and organ dysfunction. There is, however, a concurrent anti-inflammatory response that results in hyporesponsiveness of innate and adaptive immune cells. When severe, this response is termed immunoparalysis and is known to be associated with prolonged organ dysfunction, increased risk for nosocomial infection, and death in septic adults and children. Sepsis-induced immune suppression can be defined in the laboratory by reduced whole blood ex vivo - stimulated cytokine production capacities, reduced expression of human leukocyte antigen (HLA)-DR on circulating monocytes, and reduced absolute cell counts. While anti-inflammatory therapies have largely been unsuccessful at improving outcomes from adult and pediatric sepsis, the use of immunostimulatory therapies such as granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with sepsis-induced immunoparalysis shows promise. A greater understanding of the risk factors for immunoparalysis along with the development and execution of immunophenotype-specific clinical trials of strategies to optimize innate and adaptive immune function are needed to further improve outcomes in septic children.

Keywords: TNF α; HLA-DR; immune; modulation; pediatric; sepsis.

Conflict of interest statement

Conflict of Interest None declared.

Figures

Fig. 1
Fig. 1
Schematic of the dynamic inflammatory response to sepsis. CARS, compensatory anti-inflammatory response syndrome; SIRS, systemic inflammatory response syndrome.
Fig. 2
Fig. 2
Reversal of pediatric sepsis-induced immunoparalysis using GM-CSF. Treatment with GM-CSF (open circles) was associated with more rapid and more robust restoration of the TNF α response compared with standard therapy (dark squares) in a small RCT in children with sepsis-induced MODS and immunoparalysis ( n -14; adapted from Hall, 2011 2 ). * p  < 0.05. Note: TNF α response values from healthy children are approximately 1,000 pg/mL. GM-CSF, granulocyte macrophage colony stimulating factor; MODS, multiple organ dysfunction syndrome.

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