Intravenous delivery of granulocyte-macrophage colony stimulating factor impairs survival in lipopolysaccharide-induced sepsis

Cell-based therapies with bone marrow-derived progenitor cells (BMDPC) lead to an improved clinical outcome in animal sepsis models. In the present study we evaluated the ability of granulocyte macrophage-colony stimulating factor (GM-CSF) to mobilize BMDPC in a lipopolysaccharide (LPS)-induced seps...

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Bibliographic Details
Published in:PloS one 2019-06, Vol.14 (6), p.e0218602-e0218602
Main Authors: Krebs, Jörg, Hillenbrand, Alexander, Tsagogiorgas, Charalambos, Patry, Christian, Tönshoff, Burkhard, Yard, Benito, Beck, Grietje, Rafat, Neysan
Format: Article
Language:English
Subjects:
Anesthesiology
Animal models
Animals
Biology and Life Sciences
Bone marrow
Cell survival
Cells (biology)
Cells, Cultured
Chlorides
Chlorine compounds
Colonies
Colony-stimulating factor
Critical care
Cytokines
Cytokines - blood
Granulocyte-macrophage colony stimulating factor
Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage
Granulocyte-Macrophage Colony-Stimulating Factor - adverse effects
Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use
Granulocytes
Hospitals
In vivo methods and tests
Incubation
Infection
Inflammation
Interleukin 6
Interleukin 8
Intravenous administration
Laboratory animals
Leukocytes (granulocytic)
Leukocytes (mononuclear)
Lipopolysaccharides
Lipopolysaccharides - toxicity
Macrophage colony stimulating factor
Macrophages
Male
Medical research
Medicine
Medicine and Health Sciences
Mitogens
Monocytes - drug effects
Multiple organ dysfunction syndrome
Osteoprogenitor cells
Pediatrics
Peripheral blood mononuclear cells
Rats
Rats, Wistar
Research and Analysis Methods
Rodents
Sepsis
Sepsis - drug therapy
Sepsis - etiology
Sodium
Sodium chloride
Spleen
Spleen - cytology
Spleen - drug effects
Stem cells
Survival
Transplants & implants
Weight loss
Weight reduction
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Summary:Cell-based therapies with bone marrow-derived progenitor cells (BMDPC) lead to an improved clinical outcome in animal sepsis models. In the present study we evaluated the ability of granulocyte macrophage-colony stimulating factor (GM-CSF) to mobilize BMDPC in a lipopolysaccharide (LPS)-induced sepsis model and thereby its potential as a novel treatment strategy. Male Wistar rats received LPS (25μg/kg/h for 4 days) intravenously and were subsequently treated with GM-CSF 12.5μg/kg (0h,24h,48h,72h). As control groups, rats were infused with sodium chloride or GM-CSF only. Clinical and laboratory parameters, proinflammatory plasma cytokines as well as BMDPC counts were analyzed. Cytokine release by isolated peripheral blood mononuclear cells from rat spleen upon incubation with LPS, GM-CSF and a combination of both were investigated in vitro. In vivo, rats receiving both LPS and GM-CSF, showed a reduced weight loss and increased mobilization of BMDPC. At the same time, this regime resulted in an increased release of proinflammatory cytokines (IL-6, IL-8) and a significantly increased mortality. In vitro, the combination of LPS and GM-CSF showed a significantly increased IL-6 release upon incubation compared to incubation with LPS or GM-CSF alone. GM-CSF did not have a beneficial effect on the clinical course in our LPS-induced sepsis model. It synergistically promoted inflammation with LPS and probably thereby impaired survival.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0218602