MARROW GRANULOCYTE-MACROPHAGE PROGENITOR-CELL RESPONSE TO BURN INJURYAS MODIFIED BY ENDOTOXIN AND INDOMETHACIN

The production and release of granulocytes and macrophages are signifi cantly impaired following burn injury and infection. in an attempt to determine the factors responsible for these adverse effects and their potential treatments, we performed a series of studies in mice analyzi ng the bone marrow response to burn wound infection. The proliferative response of the marrow granulocyte-macrophage progenitor cell (GM-CFC ) in male BDF1 mice undergoing a dorsal scald burn or burn wound seedi ng with 1000 colony forming units of Pseudomonas aeruginosa was determ ined on day 3 postburn using a clonal culture of GM-CFC. Mice with inf ected burn wounds had a rate of GM-CFC proliferation that was 50% that of noninfected animals and levels of circulating colony stimulating a ctivity (CSA) 30% those of controls (p = 0.006). Similar suppression o f marrow proliferative status could be replicated with the administrat ion of endotoxin to normal or burned animals as had been observed for burn-infected animals. The administration of indomethacin (5 mg/kg.day ) substantially restored the GM-CFC proliferation in mice with infecte d burns as well as in animals given endotoxin. Indomethacin-treated an imals had CSA values 244% those of untreated burn-infected animals (p = 0.016). We take these observations to suggest that suppression of my elopoiesis in burn-infected animals is related in part to endotoxin-st imulated production of prostaglandin mediators that altered myeloid pr oliferation and was responsive to cyclooxygenase blockade.