Granulocyte colony-stimulating factor alters the systemic metabolomic profile in healthy donors

INTRODUCTION: Peripheral blood stem cells mobilized by granulocyte colony-stimulating factor (G-CSF) from healthy donors are commonly used for allogeneic stem cell transplantation. The effect of G-CSF administration on global serum metabolite profiles has not been investigated before. OBJECTIVES: This study aims to examine the systemic metabolomic profiles prior to and following administration of G-CSF in healthy adults. METHODS: Blood samples were collected from 15 healthy stem cell donors prior to and after administration of G-CSF 10 µg/kg/day for 4 days. Using a non-targeted metabolomics approach, metabolite levels in serum were determined using ultrahigh performance liquid chromatography-tandem mass spectrometry and gas chromatography/mass spectrometry. RESULTS: Comparison of the metabolite profiles of donors before and after G-CSF treatment revealed 239 metabolites that were significantly altered. The major changes of the metabolite profiles following G-CSF administration included alteration of several fatty acids, including increased levels of several medium and long-chain fatty acids, as well as polyunsaturated fatty acids; while there were lower levels of other lipid metabolites such as phospholipids, lysolipids, sphingolipids. Furthermore, there were significantly lower levels of several amino acids and/or their metabolites, including several amino acids with known immunoregulatory functions (methionine, tryptophan, valine). Lastly, the levels of several nucleotides and nucleotide metabolites (guanosine, adenosine, inosine) were also decreased after G-CSF administration, while methylated products were increased. Some of these altered products/metabolites may potentially have angioregulatory effects whereas others may suggest altered intracellular epigenetic regulation. CONCLUSION: Our results show that G-CSF treatment alters biochemical serum profiles, in particular amino acid, lipid and nucleotide metabolism. Additional studies are needed to further evaluate the relevance of these changes in healthy donors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-016-1139-x) contains supplementary material, which is available to authorized users.