Watanabe T, Kawano Y, Kanamaru S, Onishi T, Kaneko S, Wakata Y, Nakagawa R, Makimoto A, Kuroda Y, Takaue Y, Talmadge J E
Department of Pediatrics, Tokushima University School of Medicine, Tokushima, Japan.
Blood. 1999 Feb 15;93(4):1157-63.
The relationship between stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) and the endogenous production of interleukin-8 (IL-8), macrophage inflammatory protein-1alpha (MIP-1alpha), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) was studied in normal donors for allogeneic peripheral blood stem cell (PBSC) transplantation. G-CSF was administered to 20 normal donors at a dose of 10 microg/kg/d for 5 days with aphereses on days 5 and 6 of G-CSF treatment. Cytokine serum levels were measured using an enzyme-linked immunosorbent assay (ELISA) before and during G-CSF treatment. Before treatment, the average level of IL-8 was 7.1 pg/mL, increasing to 207.0 pg/mL on day 5 and 189.1 pg/mL on day 6. Serum IL-8 levels correlated CD34(+) cell numbers (P =.0151 and P =.0005 on days 5 and 6, respectively) and colony-forming unit-granulocyte-macrophage (CFU-GM) numbers (P =.0019 and P =.0010 on days 5 and 6, respectively). Furthermore, preapheresis serum IL-8 levels correlated with the yield of CD34(+) cells (P =.0027). In contrast, before treatment, the average levels of MIP-1alpha, TNF-alpha, and IFN-gamma were 70.1, 4.03, and 3.84 pg/mL, respectively, and no significant changes in the levels of these cytokines were observed during G-CSF treatment. These studies suggest that IL-8 production may be critical to G-CSF-induced stem cell mobilization, although the underlying mechanism could not be clarified.
在异基因外周血干细胞(PBSC)移植的正常供体中,研究了粒细胞集落刺激因子(G-CSF)动员干细胞与白细胞介素-8(IL-8)、巨噬细胞炎性蛋白-1α(MIP-1α)、肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)内源性产生之间的关系。对20名正常供体给予G-CSF,剂量为10μg/kg/d,共5天,并在G-CSF治疗的第5天和第6天进行单采。在G-CSF治疗前和治疗期间,使用酶联免疫吸附测定(ELISA)测量细胞因子血清水平。治疗前,IL-8的平均水平为7.1 pg/mL,在第5天增加到207.0 pg/mL,在第6天增加到189.1 pg/mL。血清IL-8水平与CD34(+)细胞数量相关(第5天和第6天分别为P = 0.0151和P = 0.0005)以及集落形成单位-粒细胞-巨噬细胞(CFU-GM)数量相关(第5天和第6天分别为P = 0.0019和P = 0.0010)。此外,单采前血清IL-8水平与CD34(+)细胞产量相关(P = 0.0027)。相比之下,治疗前,MIP-1α、TNF-α和IFN-γ的平均水平分别为70.1、4.03和3.84 pg/mL,在G-CSF治疗期间未观察到这些细胞因子水平的显著变化。这些研究表明,IL-8的产生可能对G-CSF诱导的干细胞动员至关重要,尽管其潜在机制尚不清楚。