Severity of burn injury and sepsis determines the cytokine responses of bone marrow progenitor-derived macrophages.

BACKGROUND: Although thermal injury and sepsis result in enhanced monocytopoiesis, the functional characteristics of macrophages that develop in the microenvironment of burn and sepsis are unknown. Here we compare cytokine responses of bone marrow progenitor-derived macrophages (BMO) and peritoneal macrophages (PMO) after graded levels of thermal injury and sepsis. METHODS: Mice were randomly divided into sham (S), burn (B), and burn sepsis (BS) groups. The mild injury group received either a 7-second dorsal scald burn alone or in combination with 1,000 colony forming units (CFU) Pseudomonas aeruginosa at the wound site. The severe injury group was subjected to a 10-second burn with or without inoculation of 5,000 CFU P. aeruginosa. ER-MP12+ progenitors were separated from bone marrow cells 72 hour after injury. Macrophage colony stimulating factor (M-CSF) and Granulocyte-macrophage colony stimulating factor (GM-CSF) responsive clonogenic potentials, and lipopolysaccharide (LPS)-stimulated cytokine production were determined. RESULTS: In mild injury and sepsis, GM-CSF and M-CSF responsive clonal growth of ER-MP12+ progenitors was enhanced in the B and BS groups compared with the S group. M-CSF responsive colony growth in severe sepsis was significantly higher than that in all the other groups. LPS-stimulated tumor necrosis factor-alpha and Interleukin-6 levels were higher in the B and BS groups compared with the S group. Severe injury and sepsis attenuated this response significantly. The cytokine responses of PMO from both injury groups were similar to that of BMO. CONCLUSION: Severity of burn injury and the magnitude of sepsis influence the cytokine responses of BMO and PMO in a similar manner suggesting the microenvironment of burn injury and sepsis profoundly influence the functional phenotype of BMO.