Effect of granulocyte-macrophage colony-stimulating factor on the immune response of circulating monocytes after severe trauma

Objective: Severe injury compromises functions of the antigen-presenting immune cells, resulting in an increased vulnerability toward bacterial sepsis. Support of the immune capabilities contributes a desirable therapeutic option in high-risk patients. Factors possessing immunostimulating properties such as granulocyte-macrophage colony-stimulating factor (GM-CSF) may serve as potential tools to compensate immunosuppression caused by severe trauma. In the present study, therefore, GM-CSF was examined with regard to its capacity to overcome trauma-induced down-regulation of immune functions. Design: Prospective clinical experimental study. Setting: University hospital intensive care unit and research facility. Patients: Severely injured patients with >25 points on the Injury Severity Score. Interventions. Blood samples of severely injured patients were incubated in vitro with 10 ng/mL GM-CSF for 6 hrs. Measurements: Human leukocyte antigen (HLA)-DR expression on monocytes was analyzed by flow cytometry, lipopolysaccharide-induced tumor necrosis factor (TNF)alpha and interleukin-10 production of blood samples was measured by means of enzyme-linked immunoabsorbent assay. Main Results., Compared with blood specimens of healthy donors, ex vivo endotoxin-induced TNFalpha production and HLA-DR expression on monocytes were significantly reduced in blood of trauma patients. Ex vivo treatment of blood specimens with GM-CSF increased HLA-DR expression and TNFalpha production stimulated by lipopolysaccharides in both healthy volunteers and patients on day 1 after trauma. Blood samples of patients with an uneventful recovery showed nearly normal TNFa. synthesis and HLA-DR expression after 2-3 wks, whereas TNFalpha production and HLA-DR expression of patients with sepsis and multiple organ failure remained at low levels. In the sepsis/multiple organ failure group, GM-CSF also enhanced HLA-DR expression and TNFalpha production, although the levels of the volunteers' blood were not reached. Conclusions. The presented data show that trauma- and sepsis-induced depression of monocyte functions can be counteracted by GM-CSF in vitro, suggesting that this substance may serve as support of immune functions in severely injured patients.