GM-CSF ameliorates inflammation from Pseudomonas aeruginosa in a juvenile mouse model of burn injury.

Pediatric burn injury induces concurrent systemic inflammation and immune dysfunction, which is associated with adverse clinical outcomes (e.g. infections). For that reason, immunomodulating therapies, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), have been of great interest to augment the immune response following burn injury. Our goal was to explore the effectiveness of GM-CSF after burn injury using a well-established, clinically relevant, juvenile mouse model of scald burn injury with bacterial infection. GM-CSF was administered intraperitoneally 3 d post-burn injury followed by a subcutaneous Pseudomonas aeruginosa inoculation at the burn wound site on post injury day 4. Seven days post-burn injury, spleen, lung, blood, and burn tissue samples were obtained to assess number of leukocytes, local and systemic cytokine concentrations, soluble protein concentrations, and bacterial clearance. Burn injury with Pseudomonas infection resulted in increased proinflammatory cytokine levels systemically and within the local burn wound and increased systemic soluble B and T lymphocyte attenuator concentrations while it decreased systemic CD27 and immune cells compared with burn alone. Treatment with a single dose of GM-CSF given prior to infection effectively ameliorated inflammation and soluble B and T lymphocyte attenuator, increased innate immune cells, decreased bacterial load, and indicated an increased wound healing environment compared with those mice who did not receive treatment. These findings provide early evidence that GM-CSF may represent a viable treatment option to improve clinical outcomes after pediatric burn injury.