Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis
Axel Nierhaus, Barbara Montag, Nicole Timmler, Daniel P. Frings, Kai Gutensohn, Roman Jung, Claus G. Schneider, Werner Pothmann, Anne K. Brassel, Jochen Schulte am Esch
Pages 646 - 651
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.
Prospective, non-randomised observational study.
Two anaesthesiological intensive care units of a university hospital.
Administration of a daily dose of 5 µg/kg rhGM-CSF over a period of 3 days.
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.
Measurements and results
Mean MFI was 69.4±13.2 24 h before and 56.7±8.2 on the day of the administration of 5 µg/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-α 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%.
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-α response, this upregulation of a monocytic activation marker is paralleled by a functional recovery.
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