title: Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis.
abstract: OBJECTIVE
  To evaluate the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on immunoparalysis as defined by a sustained decrease of HLA-DR expression on monocytes in patients with severe sepsis.
  
  
  METHODS
  Prospective, non-randomised observational study.
  
  
  METHODS
  Two anaesthesiological intensive care units of a university hospital.
  
  
  METHODS
  Administration of a daily dose of 5 micro g/kg rhGM-CSF over a period of 3 days.
  
  
  METHODS
  Nine consecutive patients with severe sepsis and a documented HLA-DR expression on peripheral monocytes of less than 150 mean fluorescence intensity (MFI) over a period of at least 48 h prior to intervention.
  
  
  RESULTS
  Mean MFI was 69.4+/-13.2 24 h before and 56.7+/-8.2 on the day of the administration of 5 micro g/kg rhGM-CSF. Within 24 h a significant increase of HLA-DR expression to a mean of 327.7+/-78.8 MFI was observed in all patients. This increase was maintained on days 2-10. It was accompanied by a significant rise in white blood count. The ex vivo TNF-alpha production in whole blood after lipopolysaccharide (LPS)-stimulation increased significantly from a mean of 82+/-29.2 pg/ml to 793+/-546.8 pg/ml. Apart from febrile reactions in two patients, no side effects were recorded. No increases of pro-inflammatory markers (IL-6, C-reactive protein, LPS-binding protein, procalcitonin) were observed. SOFA values before and after rhGM-CSF did not differ significantly. The mortality rate was 33%.
  
  
  CONCLUSIONS
  This preliminary study demonstrates that rhGM-CSF upregulates HLA-DR expression on monocytes in septic patients with multi-organ dysfunction. Moreover, with the concomitant increase of the ex vivo whole blood TNF-alpha response, this upregulation of a monocytic activation marker is paralleled by a functional recovery.
authors.affiliation: Department of Anaesthesiology, University Hospital Eppendorf, 20246, Hamburg, Germany. nierhaus@uke.uni-hamburg.de
authors.forename: Axel
authors.initials: A
authors.lastname: Nierhaus
authors.forename: Barbara
authors.initials: B
authors.lastname: Montag
authors.forename: Nicole
authors.initials: N
authors.lastname: Timmler
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Frings
authors.forename: Kai
authors.initials: K
authors.lastname: Gutensohn
authors.forename: Roman
authors.initials: R
authors.lastname: Jung
authors.forename: Claus G
authors.initials: CG
authors.lastname: Schneider
authors.forename: Werner
authors.initials: W
authors.lastname: Pothmann
authors.forename: Anne K
authors.initials: AK
authors.lastname: Brassel
authors.forename: Jochen
authors.initials: J
authors.lastname: Schulte Am Esch
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D009102:Multiple Organ Failure / Q000097:blood* / Q000188:drug therapy; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000494:pharmacology*; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy; D018709:Statistics, Nonparametric; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor