Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis.
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.
Nierhaus
Axel
A
Department of Anaesthesiology, University Hospital Eppendorf, 20246, Hamburg, Germany. nierhaus@uke.uni-hamburg.de
Montag
Barbara
B
Timmler
Nicole
N
Frings
Daniel P
DP
Gutensohn
Kai
K
Jung
Roman
R
Schneider
Claus G
CG
Pothmann
Werner
W
Brassel
Anne K
AK
Schulte Am Esch
Jochen
J
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
D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor