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.


METHODS
Prospective clinical experimental study.


METHODS
University hospital intensive care unit and research facility.


METHODS
Severely injured patients with >25 points on the Injury Severity Score.


METHODS
Blood samples of severely injured patients were incubated in vitro with 10 ng/mL GM-CSF for 6 hrs.


METHODS
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.


RESULTS
Compared with blood specimens of healthy donors, ex vivo endotoxin-induced TNF alpha 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 TNF alpha 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 TNF alpha synthesis and HLA-DR expression after 2-3 wks, whereas TNF alpha 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 TNF alpha 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.
Flohé
Sascha
S
Department of Trauma Surgery, University Hospital of Essen, Germany.
Lendemans
Sven
S
Selbach
Christian
C
Waydhas
Christian
C
Ackermann
Marcus
M
Schade
F Ulrich
FU
Kreuzfelder
Ernst
E
D000328:Adult; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006684:HLA-DR Antigens / Q000097:blood / Q000276:immunology*; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014947:Wounds and Injuries / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism
D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor