Rinehart J, Keville L, Clayton S, Figueroa J A
Department of Medicine, Scott & White Clinic and Memorial Hospital, Texas A&M University Health Sciences Center, College of Medicine, Temple 76508, USA.
Exp Hematol. 1997 May;25(5):405-12.
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.
皮质类固醇改变造血作用的机制尚未完全阐明。我们采用无内毒素系统，研究了琥珀酸氢化可的松（HCS）增强人骨髓（BM）粒-巨噬细胞集落形成单位（CFU-GM）增殖的机制。白细胞介素-1β（IL-1）（1 ng/mL）、粒-巨噬细胞集落刺激因子（GM-CSF）（1 ng/mL）或二者联合应用时，除非向培养物中添加HCS（每4×10⁵个BM单个核细胞形成80 - 125个集落，而未添加HCS时为10 - 25个集落），否则诱导的CFU-GM增殖极少。检测用IL-1 + GM-CSF ± HCS孵育单个核细胞产生的上清液诱导CFU-GM增殖的能力：除非存在HCS，IL-1和/或GM-CSF无法诱导出能够支持CFU-GM增殖的上清液。对单个核细胞亚群产生的细胞因子进行分析表明，HCS显著增强了IL-1诱导的单核细胞分泌粒细胞（G）-CSF。此外，诱导G-CSF释放所需的IL-1最小有效浓度降低了10倍（从1 ng/mL降至0.1 ng/mL），并且在IL-1浓度为1 ng/mL时，释放的G-CSF增加了5倍。相反，HCS抑制了IL-1诱导的单核细胞分泌肿瘤坏死因子（TNF）。HCS在生理浓度（10 μg/dL）时增强G-CSF分泌，而孕酮则无此作用。单独的HCS对G-CSF分泌或mRNA表达无影响，而IL-1 + HCS使G-CSF mRNA水平增加了3倍。这些数据首次表明，皮质类固醇增加了淋巴细胞生成细胞因子-生长因子系统重要成分的分泌。
