Granulocyte colony-stimulating factor (G-CSF) induces the production of cytokines in vivo

Granulocyte colony-stimulating factor (G-CSF) is a haematopoietic growth factor required for the proliferation and differentiation of haematopoietic precursors of neutrophil granulocytes and is now used to overcome congenital and acquired neutropenia. In addition to increasing the numbers of neutrophils in vivo and modulating neutrophil functions, G-CSF mag induce the production of cytokines such as tumour necrosis factor alpha (TNF-alpha). In the present study the plasma levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in six healthy volunteers given G-CSF at 10 mu g/kg once daily for 6 d were measured and found to be elevated. The elevated levels (P < 0.05) were detected on day 2, peaked on days 6-7 and returned to baseline on day 12. In vitro, G-CSF did not enhance the secretion of TNF-alpha and GM-CSF from mononuclear cells, whole blood or endothelial cells. However, in the co-presence of whole blood and endothelial cells, the secretion of TNF-alpha was significantly enhanced by G-CSF at low concentrations, The GM-CSF secretion, however, was unaltered. G-CSF pretreatment of whole blood suppressed lipopolysaccharide (LPS)-induced secretion of TNF-alpha and GM-CSF in a dose-dependent manner, These results together with our previous findings suggest that G-CSF induces the production of TNF-alpha and GM-CSF in vivo, and that this production may be due to the co-effects of endothelial cells and whole blood under the influence of G-CSF through an as yet unknown network of cells and cytokines, Treatment of whole blood with G-CSF suppresses LPS-induced secretion of TNF-alpha and GM-CSF.