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

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 inte...

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Published in:	Intensive care medicine Vol. 29; no. 4; pp. 646 - 651
Main Authors:	NIERHAUS, Axel, MONTAG, Barbara, TIMMLER, Nicole, FRINGS, Daniel P, GUTENSOHN, Kai, JUNG, Roman, SCHNEIDER, Claus G, POTHMANN, Werner, BRASSEL, Anne K, SCHULTE AM ESCH, Jochen
Format:	Journal Article
Language:	English
Published:	Heidelberg Springer 01-04-2003 Berlin Springer Nature B.V
Subjects:	Adult Aged Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Biological and medical sciences Emergency and intensive care: infection, septic shock Female Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology HLA-DR Antigens - blood Humans Intensive care medicine Male Medical sciences Middle Aged Monocytes - cytology Monocytes - metabolism Multiple Organ Failure - blood Multiple Organ Failure - drug therapy Prospective Studies Recombinant Proteins - pharmacology Sepsis - blood Sepsis - drug therapy Statistics, Nonparametric Time Factors Tumor Necrosis Factor-alpha - metabolism Human Intensive care Monocyte Septicemia HLA-DR-System Cytokine Biological marker Intensive care unit Granulocyte-macrophage colony-stimulating factor (GM-CSF) Monocytes HLA-DR Polypeptide Sepsis Severity score Innate immune response Tumor necrosis factor α Granulocyte macrophage colony stimulating factor
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Summary:	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 micro g/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. 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%. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0342-4642 1432-1238
DOI:	10.1007/s00134-003-1666-6