title: Corticosteroids alter hematopoiesis in vitro by enhancing human monocyte secretion of granulocyte colony-stimulating factor.
abstract: The mechanism of corticosteroid alteration of hematopoiesis is not completely elucidated. Employing an endotoxin free system, we examined the mechanisms by which hydrocortisone succinate (HCS) enhanced human bone marrow (BM) colony forming unit granulocyte-macrophage (CFU-GM) proliferation. Interleukin-1beta (IL-1) (1 ng/mL), granulocyte-macrophage colony-stimulating factor (GM-CSF) (1 ng/mL), or the combination, induced minimal CFU-GM proliferation unless HCS was added to the cultures (10-25 vs. 80-125 colonies/4x10(5) BM mononuclear cells). Supernatants produced by incubating mononuclear cells with IL-1 + GM-CSF +/- HCS were examined for their capacity to induce CFU-GM proliferation: IL-1 and/or GM-CSF failed to induce supernatants capable of supporting CFU-GM proliferation unless HCS was present. Analysis of the cytokines produced by mononuclear cell subpopulations demonstrated that HCS markedly enhanced IL-1-induced monocyte secretion of granulocyte (G)-CSF. Furthermore, the minimal effective concentration of IL-1 required to induce G-CSF release was reduced 10-fold (from 1 to 0.1 ng/mL) and the G-CSF released was increased 5-fold at an IL-1 concentration of 1 ng/mL. In contrast, IL-1-induced monocyte secretion of tumor necrosis factor (TNF) was inhibited by HCS. HCS enhanced G-CSF secretion at physiologic concentrations (10 microg/dL), whereas progesterone had no effect. HCS alone had no effect on G-CSF secretion or mRNA expression while IL-1+HCS resulted in a 3-fold increase in G-CSF mRNA levels. These data suggest for the first time that corticosteroids increase secretion of an essential component of the lymphohematopoietic cytokine-growth factor system.
authors.affiliation: Department of Medicine, Scott & White Clinic and Memorial Hospital, Texas A&M University Health Sciences Center, College of Medicine, Temple 76508, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rinehart
authors.forename: L
authors.initials: L
authors.lastname: Keville
authors.forename: S
authors.initials: S
authors.lastname: Clayton
authors.forename: J A
authors.initials: JA
authors.lastname: Figueroa
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004731:Endotoxins / Q000032:analysis / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D007700:Kinetics; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000378:metabolism*
chemical_list: D000305:Adrenal Cortex Hormones; D003470:Culture Media; D004731:Endotoxins; D007375:Interleukin-1; D016179:Granulocyte Colony-Stimulating Factor; D003609:Dactinomycin; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone