Mangan K F, Mullaney M T, Barrientos T D, Kernan N A
Department of Medicine, Temple University School of Medicine, Philadelphia, PA.
Blood. 1993 Apr 1;81(7):1915-22.
Engraftment of marrow following autologous or allogeneic bone marrow transplantation (BMT) may be influenced by quantity and function of stem cells. T lymphocytes, supporting microenvironmental cells, and hematopoietic growth factors (HGF). To elucidate the physiologic role of interleukin-3 (IL-3) in the engraftment process, serum IL-3 levels were measured in over 400 samples from 77 transplant recipients before and for up to 3 weeks following transplantation using a novel enzyme-linked immunoabsorbent assay (ELISA) with a sensitivity of > or = 78 pg/mL. Thirty-seven patients received two to three log T-cell-depleted allografts. In the remaining 40 patients (18 autologous marrow, 12 allogeneic marrow, and 10 autologous peripheral blood [PB] stem cell), T cells were not depleted (non-TCD) from the grafts. A burst of IL-3 (peak levels, 1,500 to 6,000 pg/mL) was detected in the immediate posttransplant period between day 0 and day 14 in all non-TCD recipients and in 21 of 37 (57%) of TCD recipients. A strong inverse relationship between IL-3 levels and absolute neutrophil count (ANC) was observed in both non-TCD recipients (r = -.796) and in TCD recipients (r = -.897). However, both peak IL-3 levels and mean IL-3 levels from day 0 through 14 were significantly lower in TCD recipients compared with either autologous or unmodified allogeneic marrow recipients (P < .01). The lowest peak or mean day 0 through 14 IL-3 levels were observed in matched related recipients undergoing the most aggressive (2.5 to 3.0 log) T-cell-depleted BMT. Autografted patients receiving blood stem cell transplants alone or posttransplant granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) also had significantly lower peak IL-3 levels (P < .01). In patients receiving TCD grafts, administration of antithymocyte globulin (ATG) posttransplant significantly increased peak IL-3 levels compared with patients not treated with ATG (P < .04). This study shows that endogenous release of IL-3 is strongly associated with myeloid engraftment and inversely related to ANC. Removal of T lymphocytes from donor marrow or acceleration of engraftment by use of stem cells or growth factors appears to blunt the endogenous release of IL-3 whereas use of ATG posttransplant increases IL-3 release.
自体或异体骨髓移植（BMT）后骨髓的植入可能受到干细胞数量和功能、T淋巴细胞、支持性微环境细胞以及造血生长因子（HGF）的影响。为了阐明白细胞介素-3（IL-3）在植入过程中的生理作用，使用一种灵敏度≥78 pg/mL的新型酶联免疫吸附测定（ELISA）法，对77名移植受者移植前及移植后长达3周的400多个样本中的血清IL-3水平进行了检测。37名患者接受了两到三个对数级T细胞清除的同种异体移植物。在其余40名患者（18名自体骨髓、12名同种异体骨髓和10名自体外周血[PB]干细胞）中，移植物中的T细胞未被清除（非TCD）。在所有非TCD受者以及37名TCD受者中的21名（57%）移植后0至14天的即刻时期检测到IL-3的爆发（峰值水平为1500至6000 pg/mL）。在非TCD受者（r = -0.796）和TCD受者（r = -0.897）中均观察到IL-3水平与绝对中性粒细胞计数（ANC）之间存在强烈的负相关关系。然而，与自体或未处理的同种异体骨髓受者相比，TCD受者从第0天到第14天的IL-3峰值水平和平均IL-3水平均显著较低（P < 0.01）。在接受最激进（2.5至3.0对数级）T细胞清除BMT的匹配相关受者中观察到第0天到第14天IL-3的最低峰值或平均水平。仅接受血干细胞移植或移植后接受粒细胞集落刺激因子（G-CSF）或粒细胞-巨噬细胞集落刺激因子（GM-CSF）的自体移植患者的IL-3峰值水平也显著较低（P < 0.01）。在接受TCD移植物的患者中，移植后给予抗胸腺细胞球蛋白（ATG）的患者与未接受ATG治疗的患者相比，IL-3峰值水平显著升高（P < 0.04）。这项研究表明，IL-3的内源性释放与髓系植入密切相关，且与ANC呈负相关。从供体骨髓中去除T淋巴细胞或使用干细胞或生长因子加速植入似乎会抑制IL-3的内源性释放，而移植后使用ATG会增加IL-3的释放。
