PMID- 14530752 OWN - NLM STAT- MEDLINE DCOM- 20031105 LR - 20220311 IS - 0090-3493 (Print) IS - 0090-3493 (Linking) VI - 31 IP - 10 DP - 2003 Oct TI - Effect of granulocyte-macrophage colony-stimulating factor on the immune response of circulating monocytes after severe trauma. PG - 2462-9 AB - 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 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. FAU - Flohe, Sascha AU - Flohe S AD - Department of Trauma Surgery, University Hospital of Essen, Germany. FAU - Lendemans, Sven AU - Lendemans S FAU - Selbach, Christian AU - Selbach C FAU - Waydhas, Christian AU - Waydhas C FAU - Ackermann, Marcus AU - Ackermann M FAU - Schade, F Ulrich AU - Schade FU FAU - Kreuzfelder, Ernst AU - Kreuzfelder E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Crit Care Med JT - Critical care medicine JID - 0355501 RN - 0 (HLA-DR Antigens) RN - 0 (Tumor Necrosis Factor-alpha) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Adult MH - Female MH - Granulocyte-Macrophage Colony-Stimulating Factor/*therapeutic use MH - HLA-DR Antigens/blood/*immunology MH - Humans MH - Injury Severity Score MH - Male MH - Middle Aged MH - Prospective Studies MH - Tumor Necrosis Factor-alpha/*biosynthesis MH - *Wounds and Injuries/drug therapy/immunology/metabolism EDAT- 2003/10/08 05:00 MHDA- 2003/11/06 05:00 CRDT- 2003/10/08 05:00 PHST- 2003/10/08 05:00 [pubmed] PHST- 2003/11/06 05:00 [medline] PHST- 2003/10/08 05:00 [entrez] AID - 10.1097/01.CCM.0000089640.17523.57 [doi] PST - ppublish SO - Crit Care Med. 2003 Oct;31(10):2462-9. doi: 10.1097/01.CCM.0000089640.17523.57.