Macrophage mediated suppression of granulocyte and macrophage growth after burn wound infection reversal by means of anti-PGE2

The production and release of granulocytes and macrophages, crucial elements of the host defense system, are significantly impaired after burn injury and sepsis. Prostaglandin E-2 (PGE(2)) is known to be myelosuppressive. We hypothesized that the macrophages contributed to myelopoietic suppression by means of increased PGE(2) production, which is induced by thermal injury and sepsis. In this study, peritoneal macrophages were elicited at day 3 from normal mice and from mice who underwent a 15% total body surface area dorsal scald burn with or without Pseudomonas aeruginosa burn wound infection. The macrophages were incubated with or without endotoxin and with or without PGE(2) polyclonal antiserum (anti-PGE(2)) for 18 hours. Macrophage supernatants mere then used in co-cultures of bone marrow cells in a clonogenic assay of granulocyte-macrophage colony-forming cells (GM-CFCs) to determine the effect of burn wound infection on the alteration of the proliferative status of the GM-CFCs. Burn mound infection and endotoxin both caused marked reductions in GM-CFC growth in culture (20%-40% as compared with normal, P < .05-.01). The inhibition of GM-CFC growth induced by burn, burn plus infection, or endotoxin was significantly reversed by the addition of anti-PGE(2) to the cultures (30%-40% increase in GM-CFC colony growth as compared with cultures without anti-PGE(2)). These results suggest that PGE2 is a key mediator in the gram-negative sepsis-induced macrophage suppression of granulocyte and macrophage production. The ability of anti-PGE(2) to neutralize PGE(2) activity may provide a useful means of mitigating myeloid depression that follows postburn sepsis.