Krumwieh D, Weinmann E, Seiler F R
Research Laboratories of Behringwerke AG, Marburg/Lahn, W.-Germany.
Behring Inst Mitt. 1988 Aug(83):250-7.
Recent progress in molecular cloning has provided access to several major human colony-stimulating factors - GM-CSF, IL-3, G-CSF and M-CSF. Now they are available highly purified from different expression systems (e.g. yeast, E. coli, CHO cells). These molecules, acting multifunctionally in the hematopoietic system, are responsible for proliferation and differentiation of bone marrow-derived progenitor cells in vitro. First clinical studies performed with colony-stimulating factors have shown that neutropenia caused by drug-induced immunosuppression in patients with refractory cancer or autologous bone marrow transplantation was reversed using rh GM-CSF or rh G-CSF. We have investigated the effect of the consecutive administration of rh IL-3 and GM-CSF on hematopoiesis in normal cynomolgus monkeys. Whereas administration of rh IL-3 alone did not result in an increase of WBC counts, the combination therapy of rh IL-3 followed by rh GM-CSF exhibited significant synergistic effects and raised WBC numbers. Furthermore, application of both factors resulted in a platelet rise not seen when one of the factors was used alone. The response was dose dependent and implicated that the therapeutical potential of rh GM-CSF could be expanded if used in combination with rh IL-3.
分子克隆技术的最新进展使得人们能够获取几种主要的人类集落刺激因子——粒细胞-巨噬细胞集落刺激因子（GM-CSF）、白细胞介素-3（IL-3）、粒细胞集落刺激因子（G-CSF）和巨噬细胞集落刺激因子（M-CSF）。现在，它们可以从不同的表达系统（如酵母、大肠杆菌、中国仓鼠卵巢细胞）中高度纯化得到。这些分子在造血系统中发挥多种功能，负责体外骨髓来源祖细胞的增殖和分化。使用集落刺激因子进行的首批临床研究表明，在难治性癌症患者或自体骨髓移植中，由药物诱导的免疫抑制引起的中性粒细胞减少症可通过使用重组人GM-CSF（rh GM-CSF）或重组人G-CSF（rh G-CSF）得到逆转。我们研究了连续给予重组人IL-3和GM-CSF对正常食蟹猴造血功能的影响。单独给予重组人IL-3不会导致白细胞计数增加，而重组人IL-3随后给予重组人GM-CSF的联合治疗则表现出显著的协同作用并提高了白细胞数量。此外，同时应用这两种因子会导致血小板升高，而单独使用其中一种因子时则未出现这种情况。这种反应具有剂量依赖性，这意味着重组人GM-CSF与重组人IL-3联合使用时其治疗潜力可能会扩大。
