RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR TREATMENT IMPROVES MACROPHAGE SUPPRESSION OF GRANULOCYTE AND MACROPHAGE GROWTH AFTER BURN AND BURN WOUND-INFECTION

Granulocyte and macrophage production after burn injury or burn wound infection is significantly reduced and further compromised by endotoxi n (ET), Moreover, the macrophage seems to be the major source of this hone marrow suppression, We sought to determine if recombinant human g ranulocyte colony-stimulating factor (rhG-CSF), a hematopoietic growth factor that is capable of improving survival after experimental burn wound sepsis, altered postburn macrophage-mediated marrow suppression, Groups of male BDF1 mice (n = 6 to 10) receiving a 15% total body sur face area burn +/- infection (B or B + I) with Pseudomonas aeruginosa were injected with 100 ng rhG-CSF twice daily. On day 3, peritoneal-el icited macrophages (5 x 10(6) cells/mL) from either rhG-CSF-treated or control(5% dextrose in water) mice were incubated +/- ET (300 ng/mL). The resultant macrophage supernatant was added to cultures of target marrow granulocyte-macrophage progenitor cells (GM-CFC) at a volume of 1:10. The GM-CFC growth as a percentage of cultures not containing ma crophage supernatant were compared and reductions in the number of GM- CFC taken as an index of marrow suppression, Macrophages obtained from B and B + I animals reduced target GM-CFC growth, compared with macro phages from normal animals (B vs, normal animals p < 0.05). In additio n, ET-stimulated macrophages induced further bone marrow suppression f or all three groups (p < 0.01). Macrophages from granulocyte colony-st imulating factor-treated animals caused significantly less bone marrow suppression, compared with untreated animals for all groups (p < 0.05 to 0.01). Granulocyte colony-stimulating factor administration postbu rn, in addition to serving as a direct bone marrow stimulant, also alt ers the macrophage secretory profile and ameliorates macrophage-induce d bone marrow suppression.