Short-term injection of antiapoptotic cytokine combinations soon after lethal γ-irradiation promotes survival
Short-term injection of antiapoptotic cytokine combinations soon after lethal γ-irradiation promotes survival
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DOI：
10.1182/blood-2002-06-1634
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发表时间：
2003-04-01
期刊：
影响因子：
20.3
通讯作者：
Drouet, M
中科院分区：
文献类型：
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作者：
Hérodin, F;Bourin, P;Drouet, M
放射性骨髓抑制的恢复依赖于造血干细胞和祖细胞的存活和活跃的增殖/分化过程，这需要早期细胞因子的支持。单一的细胞因子或迟效生长因子治疗已被证明是无效的，以确保重建后，严重的RI损伤。这项工作旨在评价早期作用细胞因子组合的体内生存效应，这些细胞因子的抗凋亡活性已在体外得到证实：干细胞因子（SCF [S]）、FMS样酪氨酸激酶3配体（FLT-3配体[F]）、血小板生成素（TPO [T]）、白细胞介素-3（IL-3 [3]）和基质衍生因子-1（SDF-1）。对B6 D2 F1小鼠进行8戈伊铯Cs 137 γ辐射（即，30天时致死剂量为90%）的全身照射，并在照射后不久，在2小时和24小时用重组鼠细胞因子处理，每种细胞因子以每次注射50 μ g/kg腹腔内给药。所有处理诱导的30天存活率显著高于对照（存活率，8.3%）。4F（SFT 3）和5F（4F + SDF-1）是最有效的组合（分别为81.2%和87.5%），优于3F（SFT，50%），TPO单药（58.3%）和单独的SDF-1（29.2%），也优于每次注射10 μ g/kg（4F10，45.8%）或2小时单次注射50 μ g/kg（4Fs，62.5%）的4F。尽管延迟性死亡主要发生在第150天，并且可能存在长期造血功能障碍，但4F和5F的30天保护作用的一半在300天时得以保留。我们的研究结果表明，照射后的短期和长期生存取决于适当的多种细胞因子组合和最佳浓度。提出了一种紧急细胞因子方案可以应用于核事故受害者作为较长的细胞因子治疗，细胞疗法，或两者兼而有之的一部分。
Recovery from radiation-induced (RI) myelosuppression depends on hematopoietic stem and progenitor cell survival and the active proliferation/differentiation process, Which requires early cytokine support. Single cytokine or late-acting growth factor therapy has proved to be inefficient in ensuring reconstitution after severe RI damage. This work was aimed at evaluating the in vivo survival effect of combinations of early-acting cytokines whose antiapoptotic activity has been demonstrated in vitro: stem cell factor (SCF [S]), FMS-like tyrosine kinase 3 ligand (FLT-3 ligand [F]),thrombopoietin (TPO [T]), interleukin-3 (IL-3 [3]), and stromal derived factor-1 (SDF-1). B6D2F1 mice underwent total body irradiation at 8 Gy cesium Cs 137 gamma radiation (ie, lethal dose 90% at 30 days) and were treated soon after irradiation, at 2 hours and at 24 hours, with recombinant murine cytokines, each given intraperitoneally at 50 mug/kg per injection. All treatments induced 30-day survival rates significantly higher than control (survival rate, 8.3%). 4F (SFT3) and 5F (4F + SDF-1) were the most efficient combinations (81.2% and 87.5%, respectively), Which was better than 3F (SFT, 50%), TPO alone (58.3%), and SDF-1 alone (29.2%) and also better than 4F given at 10 mug/kg per injection (4F10, 45.8%) or as a 50 mug/kg single injection at 2 hours (4Fs, 62.5%). Despite delayed death occurring mainly from day 150 on and possible long-term hematopoiesis impairment, half the 30-day protective effects of 4F and 5F were preserved at 300 days. Our, results show that short- and long-term survival after irradiation depends on appropriate multiple cytokine combinations and at optimal concentrations. The proposal is made that an emergency cytokine regimen could be applied to nuclear accident victims as part of longer cytokine treatment, cell therapy, or both.