Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support.
Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support.
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DOI：
10.1182/blood.v81.9.2452.bloodjournal8192452
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发表时间：
1993-05
期刊：
影响因子：
20.3
通讯作者：
J. Rabinowitz;W. Petros;A. Stuart;W. Peters
中科院分区：
文献类型：
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作者：
J. Rabinowitz;W. Petros;A. Stuart;W. Peters
内源性细胞因子被认为介导许多生物学过程，并可能导致重组蛋白给药后出现的一些不良反应。本研究描述了高剂量化疗后内源性细胞因子暴露的模式。采用酶联免疫吸附法（ELISA）测定68例接受相同消融化疗方案（环磷酰胺、顺铂、卡莫司汀）的患者血中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、巨噬细胞集落刺激因子（M-CSF）和促红细胞生成素（EPO）的浓度。根据细胞支持（自体骨髓[BM] CSF-致敏外周血祖细胞[PBPC]）和处方生长因子（重组人粒细胞或粒细胞-巨噬细胞集落刺激因子[rHuG-CSF或rHuGM-CSF]）对患者进行分组。在PBPC和rHuG-CSF处理组中，白细胞重建最加速。IL-6、M-CSF和TNF-α浓度在用rHuGM-CSF和不用PBPC处理的组中更高。最大内源性细胞因子浓度发生在BM再输注后约12天。高浓度的EPO发生在尽管常规输血红细胞压积<42%但仍发生显著低血压的患者中。高M-CSF和IL-6水平与血小板输注需求增加相关。在发生肾或肝毒性的患者中，所有四种细胞因子的浓度均显著升高，升高以可预测的顺序发生，首先发生M-CSF升高。本报告显示，内源性细胞因子浓度可能受到细胞或CSF支持的影响，并与血小板重建和器官毒性的差异有关。
Endogenous cytokines are thought to mediate numerous biologic processes and may account for some adverse effects experienced following the administration of recombinant proteins. This study describes the pattern of endogenous cytokine exposure following high-dose chemotherapy. Blood concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor (M-CSF), and erythropoietin (EPO) were measured by enzyme-linked immunosorbent assay (ELISA) methods in 68 patients receiving the same ablative chemotherapy regimen (cyclophosphamide, cisplatin, carmustine). Patients were grouped according to cellular support (autologous bone marrow [BM] CSF-primed peripheral blood progenitor cells [PBPCs]) and prescribed growth factor (recombinant human granulocyte or granulocyte-macrophage colony-stimulating factor [rHuG-CSF or rHuGM-CSF]). Leukocyte reconstitution was most accelerated in the groups treated with PBPCs and rHuG-CSF. IL-6, M-CSF, and TNF-alpha concentrations were higher in the groups treated with rHuGM-CSF and without PBPCs. Maximal endogenous cytokine concentrations occurred approximately 12 days after BM reinfusion. High concentrations of EPO occurred in patients experiencing significant hypotension despite routine transfusions for hematocrit < 42%. High M-CSF and IL-6 levels were associated with increased platelet transfusion requirements. Concentrations of all four cytokines were significantly higher in patients experiencing renal or hepatic toxicity, with elevations occurring in a predictable sequence and M-CSF elevations occurring first. This report shows that endogenous cytokine concentrations may be influenced by either cellular or CSF support and are associated with differences in platelet reconstitution and organ toxicity.