SYNERGY OF INTERLEUKIN-1 AND GRANULOCYTE COLONY-STIMULATING FACTOR - INVIVO STIMULATION OF STEM-CELL RECOVERY AND HEMATOPOIETIC REGENERATION FOLLOWING 5-FLUOROURACIL TREATMENT OF MICE
SYNERGY OF INTERLEUKIN-1 AND GRANULOCYTE COLONY-STIMULATING FACTOR - INVIVO STIMULATION OF STEM-CELL RECOVERY AND HEMATOPOIETIC REGENERATION FOLLOWING 5-FLUOROURACIL TREATMENT OF MICE
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DOI：
10.1073/pnas.84.20.7134
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发表时间：
1987-10-01
影响因子：
11.1
通讯作者：
WARREN, DJ
中科院分区：
文献类型：
--
作者：
MOORE, MAS;WARREN, DJ
人膀胱癌细胞系5637产生造血生长因子[粒细胞和粒细胞/巨噬细胞集落刺激因子（G-CSF和GM-CSF）]和促红细胞生成素1，其与CSF协同作用，刺激原始造血干细胞在5-氟尿嘧啶处理的小鼠骨髓中形成集落。促红细胞生成素1的分子和功能特性鉴定其与白细胞介素1 α相同。（IL-1 α）。当来自5-氟尿嘧啶处理的小鼠的骨髓细胞与重组人IL-1 α悬浮培养7天时，和/或G-CSF，发现这两种因子协同作用以增强具有高和低增殖潜能的骨髓生成细胞和集落形成细胞的恢复。单独的G-CSF不能维持这些群体，但组合具有先增加后增加的刺激能力。在体内，5-氟尿嘧啶（150 mg/kg）在C3 H/HeJ小鼠中产生了严重的骨髓抑制和延迟的中性粒细胞再生长达2周。每日施用重组人G-CSF或重组人IL-1 α。在5-氟尿嘧啶处理的C3 H/HeJ和B6 D2 F1小鼠中，加速干细胞、祖细胞和血液中性粒细胞的恢复长达4天。IL-1 α.和G-CSF协同作用，减少中性粒细胞减少并加速正常中性粒细胞数量的恢复长达7天。这伴随着脾集落形成单位和骨髓和脾中的红系、髓系和巨核细胞祖细胞的加速再生，红系和粒细胞分化增强。这些结果表明IL-1和造血生长因子（如G-CSF）联合治疗化疗或放疗诱导的骨髓抑制可能具有治疗潜力。
The human bladder carcinoma cell line 5637 produces hematopoietic growth factors [granulocyte and granulocyte/macrophage colony-stimulating factors (G-CSF and GM-CSF)] and hemopoietin 1, which synergizes with CSFs to stimulate colony formation by primitive hematopoietic stem cells in 5-fluorouracil-treated mouse bone marrow. Molecular and functional properties of hemopoietin 1 identified it as identical to interleukin 1.alpha. (IL-1.alpha.). When bone marrow cells from 5-fluorouracil-treated mice were cultured in suspension for 7 days with recombinant human IL-1.alpha. and/or G-CSF, it was found that the two factors synergized to enhance recovery of myelopoietic cells and colony-forming cells of both high and low proliferative potential. G-CSF alone did not sustain these populations, but the combination had greater-then-additive stimulating capacity. In vivo, 5-fluorouracil (150 mg/kg) produced profound myelosuppression and delayed neutrophil regeneration for up to 2 weeks in C3H/HeJ mice. Daily administration of recombinant human G-CSF or recombinant human IL-1.alpha. accelereated recovery of stem cells, progenitor cells, and blood neutrophils by up to 4 days in 5-fluorouracil-treated C3H/HeJ and B6D2F1 mice. The combination of IL-1.alpha. and G-CSF acted synergistically, reducing neutropenia and accelerating recovery of normal neutrophil numbers by up to 7 days. This was accompanied by accelerated regeneration of spleen colony-forming units and erythroid, myeloid, and megakaryocytic progenitor cells in marrow and spleen, with enhanced erythroid and granulocytic differentiation. These results indicate the possible therapeutic potential of combination therapy with IL-1 and hematopoietic growth factors such as G-CSF in the treatment of chemotherapy- or radiation-induced myelosuppression.