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Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis

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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.

Design

Prospective, non-randomised observational study.

Setting

Two anaesthesiological intensive care units of a university hospital.

Intervention

Administration of a daily dose of 5 µg/kg rhGM-CSF over a period of 3 days.

Patients

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%.

Conclusion

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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Fig. 1a–c.

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Authors and Affiliations

  1. Department of Anaesthesiology, University Hospital Eppendorf, 20246, Hamburg, Germany

    Axel Nierhaus, Barbara Montag, Nicole Timmler, Daniel P. Frings, Werner Pothmann, Anne K. Brassel & Jochen Schulte am Esch

  2. Department of Transfusion Medicine, University Hospital Eppendorf, 20246 , Hamburg, Germany

    Kai Gutensohn

  3. Department of Clinical Chemistry, University Hospital Eppendorf, 20246, Hamburg, Germany

    Roman Jung

  4. Department of General Surgery, University Hospital Eppendorf, 20246 , Hamburg, Germany

    Claus G. Schneider

Authors
  1. Axel Nierhaus
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  2. Barbara Montag
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  3. Nicole Timmler
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  4. Daniel P. Frings
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  5. Kai Gutensohn
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  6. Roman Jung
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  7. Claus G. Schneider
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  8. Werner Pothmann
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  9. Anne K. Brassel
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  10. Jochen Schulte am Esch
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Corresponding author

Correspondence to Axel Nierhaus.

Additional information

Financial support came from institutional funds of the Department of Anaesthesiology, University Hospital Eppendorf, Hamburg, Germany.

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Nierhaus, A., Montag, B., Timmler, N. et al. Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis. Intensive Care Med 29, 646–651 (2003). https://doi.org/10.1007/s00134-003-1666-6

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  • DOI: https://doi.org/10.1007/s00134-003-1666-6

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