Effect of granulocyte-macrophage colony-stimulating factor on the immune response of circulating monocytes after severe trauma
作者:
Sascha Flohé,
Sven Lendemans,
Christian Selbach,
Christian Waydhas,
Marcus Ackermann,
F. Schade,
Ernst Kreuzfelder,
期刊:
Critical Care Medicine
(OVID Available online 2003)
卷期:
Volume 31,
issue 10
页码: 2462-2469
ISSN:0090-3493
年代: 2003
出版商: OVID
关键词: granulocyte-macrophage colony-stimulating factor;human leukocyte antigen–DR;tumor necrosis factor-&agr;;immunomodulation
数据来源: OVID
摘要:
ObjectiveSevere 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.DesignProspective clinical experimental study.SettingUniversity hospital intensive care unit and research facility.PatientsSeverely injured patients with >25 points on the Injury Severity Score.InterventionsBlood samples of severely injured patients were incubatedin vitrowith 10 ng/mL GM-CSF for 6 hrs.MeasurementsHuman leukocyte antigen (HLA)-DR expression on monocytes was analyzed by flow cytometry, lipopolysaccharide-induced tumor necrosis factor (TNF)&agr; and interleukin-10 production of blood samples was measured by means of enzyme-linked immunoabsorbent assay.Main ResultsCompared with blood specimens of healthy donors,ex vivoendotoxin-induced TNF&agr; production and HLA-DR expression on monocytes were significantly reduced in blood of trauma patients.Ex vivotreatment of blood specimens with GM-CSF increased HLA-DR expression and TNF&agr; 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&agr; synthesis and HLA-DR expression after 2–3 wks, whereas TNF&agr; 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&agr; production, although the levels of the volunteers’ blood were not reached.ConclusionsThe presented data show that trauma- and sepsis-induced depression of monocyte functions can be counteracted by GM-CSFin vitro, suggesting that this substance may serve as support of immune functions in severely injured patients.
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