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Int J Mol Sci. 2018 Sep 22;19(10). pii: E2886. doi: 10.3390/ijms19102886.

Immunological Heterogeneity of Healthy Peripheral Blood Stem Cell Donors-Effects of Granulocyte Colony-Stimulating Factor on Inflammatory Responses.

Author information

1
Department of Medicine, Section for Hematology, Haukeland University Hospital, 5021 Bergen, Norway. thetve@helse-bergen.no.
2
Institute of Clinical Science, Section for Hematology, University of Bergen, 5021 Bergen, Norway. thetve@helse-bergen.no.
3
Institute of Clinical Science, Section for Hematology, University of Bergen, 5021 Bergen, Norway. guro.kristin.melve@helse-bergen.no.
4
Department of Immunology and Transfusion Medicine, Haukeland University Hospital, 5021 Bergen, Norway. guro.kristin.melve@helse-bergen.no.
5
Department of Medicine, Section for Hematology, Haukeland University Hospital, 5021 Bergen, Norway. glts@helse-bergen.no.
6
Department of Medicine, Section for Hematology, Haukeland University Hospital, 5021 Bergen, Norway. abah@helse-bergen.no.
7
Department of Medicine, Section for Hematology, Haukeland University Hospital, 5021 Bergen, Norway. Annette.Brenner@uib.no.
8
Department of Medicine, Section for Hematology, Haukeland University Hospital, 5021 Bergen, Norway. brus@helse-bergen.no.
9
Institute of Clinical Science, Section for Hematology, University of Bergen, 5021 Bergen, Norway. brus@helse-bergen.no.

Abstract

Interleukin-6 (IL-6) contributes to the development of immune-mediated complications after allogeneic stem cell transplantation. However, systemic IL-6 levels also increase during granulocyte colony-stimulating factor (G-CSF) mobilization of hematopoietic stem cells in healthy donors, but it is not known whether this mobilization alters systemic levels of other IL-6 family cytokines/receptors and whether such effects differ between donors. We examined how G-CSF administration influenced C-reactive protein (CRP) levels (85 donors) and serum levels of IL-6 family cytokines/receptors (20 donors). G-CSF increased CRP levels especially in elderly donors with high pretherapy levels, but these preharvesting levels did not influence clinical outcomes (nonrelapse mortality, graft versus host disease). The increased IL-6 levels during G-CSF therapy normalized within 24 h after treatment. G-CSF administration did not alter serum levels of other IL-6-familly mediators. Oncostatin M, but not IL-6, showed a significant correlation with CRP levels during G-CSF therapy. Clustering analysis of mediator levels during G-CSF administration identified two donor subsets mainly characterized by high oncostatin M and IL-6 levels, respectively. Finally, G-CSF could increase IL-6 release by in vitro cultured monocytes, fibroblasts, and mesenchymal stem cells. In summary, G-CSF seems to induce an acute phase reaction with increased systemic IL-6 levels in healthy stem cell donors.

KEYWORDS:

C-reactive protein; Interleukin-6; acute-phase reaction; graft versus host disease; tissue and organ procurement; toll-like receptors

PMID:
30249022
PMCID:
PMC6213426
DOI:
10.3390/ijms19102886
[Indexed for MEDLINE]
Free PMC Article

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