PMID- 28553169 OWN - NLM STAT- MEDLINE DCOM- 20180301 LR - 20220409 IS - 1449-1907 (Electronic) IS - 1449-1907 (Linking) VI - 14 IP - 4 DP - 2017 TI - In vivo application of Granulocyte-Macrophage Colony-stimulating Factor enhances postoperative qualitative monocytic function. PG - 367-375 LID - 10.7150/ijms.18288 [doi] AB - BACKGROUND: Granulocyte macrophage colony-stimulating factor (GM-CSF) can be used as a potent stimulator for immune suppressed patients as defined by a decrease of human leukocyte antigen-D related expression on monocytes (mHLA-DR) after surgery. However, the exact role of GM-CSF on monocytic and T cell function is unclear. METHODS: In this retrospective randomized controlled trial (RCT) subgroup analysis, monocytic respectively T cell function and T cell subspecies of 20 immune suppressed (i.e. mHLA-DR levels below 10,000 monoclonal antibodies (mAb) per cell at the first day after surgery) patients after esophageal or pancreatic resection were analyzed. Each 10 patients received either GM-CSF (250 mug/m(2)/d) or placebo for a maximum of three consecutive days if mHLA-DR levels remained below 10,000 mAb per cell. mHLA-DR and further parameters of immune function were measured preoperatively (od) until day 5 after surgery (pod5). Statistical analyses were performed using nonparametric statistical procedures. RESULTS: In multivariate analysis, mHLA-DR significantly differed between the groups (p < 0.001). mHLA-DR was increased on pod2 (p < 0.001) and pod3 (p = 0.002) after GM-CSF application. Tumor necrosis factor-alpha (TNF-alpha) release of lipopolysaccharide (LPS) stimulated monocytes multivariately significantly differed between the groups (p < 0.008) and was increased in the GM-CSF group on pod2 (p < 0.001) and pod3 (p = 0.046). Th17/regulatory T (Treg) cell ratio was higher after GM-CSF treatment on pod2 (p = 0.041). No differences were seen in lymphocytes and T helper cell (Th)1/Th2 specific cytokine production after T cell stimulation with Concanavalin (Con) A between the groups. CONCLUSIONS: Postoperative application of GM-CSF significantly enhanced qualitative monocytic function by increased mHLA-DR and TNF-alpha release after LPS stimulation and apparently enhanced Th17/Treg ratio. Clinical trial registered with www.controlled-trials.com (ISRCTN27114642) 05 December 2008. FAU - Lachmann, Gunnar AU - Lachmann G AD - Department of Anesthesiology and Intensive Care Medicine, Campus Charite Mitte and Campus Virchow-Klinikum, Charite - Universitatsmedizin Berlin, Germany. FAU - Kurth, Johannes AU - Kurth J AD - Department of Anesthesiology and Intensive Care Medicine, Campus Charite Mitte and Campus Virchow-Klinikum, Charite - Universitatsmedizin Berlin, Germany. FAU - von Haefen, Clarissa AU - von Haefen C AD - Department of Anesthesiology and Intensive Care Medicine, Campus Charite Mitte and Campus Virchow-Klinikum, Charite - Universitatsmedizin Berlin, Germany. FAU - Yuerek, Fatima AU - Yuerek F AD - Department of Anesthesiology and Intensive Care Medicine, Campus Charite Mitte and Campus Virchow-Klinikum, Charite - Universitatsmedizin Berlin, Germany. FAU - Wernecke, Klaus-Dieter AU - Wernecke KD AD - Sostana GmbH Berlin, Germany. FAU - Spies, Claudia AU - Spies C AD - Department of Anesthesiology and Intensive Care Medicine, Campus Charite Mitte and Campus Virchow-Klinikum, Charite - Universitatsmedizin Berlin, Germany. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20170408 PL - Australia TA - Int J Med Sci JT - International journal of medical sciences JID - 101213954 RN - 0 (HLA-DR Antigens) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Adult MH - Esophagus/immunology/pathology/surgery MH - Female MH - Flow Cytometry MH - Granulocyte-Macrophage Colony-Stimulating Factor/*administration & dosage/immunology MH - HLA-DR Antigens/*immunology MH - Humans MH - Interferon-gamma/immunology MH - Lipopolysaccharides/administration & dosage MH - Male MH - Monocytes/drug effects/immunology MH - Pancreas/immunology/pathology/surgery MH - Postoperative Complications/*drug therapy/genetics/physiopathology MH - T-Lymphocyte Subsets/immunology MH - T-Lymphocytes, Regulatory/drug effects/immunology MH - Th17 Cells/drug effects/immunology MH - Tumor Necrosis Factor-alpha/*immunology PMC - PMC5436479 OTO - NOTNLM OT - GM-CSF OT - HLA-DR OT - T cell function OT - Th17/Treg ratio OT - immune stimulation OT - immune suppression OT - monocytic function COIS- Competing Interests: Deutsche Forschungsgemeinschaft (DFG SP432-1, http://www.dfg.de/, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript), Charite - Universitatsmedizin Berlin (www.charite.de, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript), statistical analysis has been supervised by Professor Klaus-Dieter Wernecke, PhD, former head of the Institute of Medical Biometry at Charite - Universitatsmedizin Berlin and owner of Sostana GmbH. We confirm that it does not alter our adherence to all policies on sharing data and materials. EDAT- 2017/05/30 06:00 MHDA- 2018/03/02 06:00 PMCR- 2017/01/01 CRDT- 2017/05/30 06:00 PHST- 2016/11/10 00:00 [received] PHST- 2017/01/30 00:00 [accepted] PHST- 2017/05/30 06:00 [entrez] PHST- 2017/05/30 06:00 [pubmed] PHST- 2018/03/02 06:00 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - ijmsv14p0367 [pii] AID - 10.7150/ijms.18288 [doi] PST - epublish SO - Int J Med Sci. 2017 Apr 8;14(4):367-375. doi: 10.7150/ijms.18288. eCollection 2017.