Effect of various interleukins (IL-1, IL-2, and IL-3) on the in vitro radioprotection of bone marrow progenitors (CFU-GM and CFU-MEG).

V S Gallicchio, B C Hulette, M J Messino, C Gass, M W Bieschke, M A Doukas
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Abstract

Radiation exposure to various systems can result in the development of severe toxicity, known as the acute radiation syndrome, with hematopoietic tissues being acutely susceptible to radiation-induced injury. Usually it is the degree of hematopoietic toxicity that determines the feasibility of further tumor control doses of therapy. Therefore the development of agents capable of protecting hematopoietic tissues could have important clinical applications. The cytokine interleukin-1 (IL-1) has been demonstrated to be an effective agent capable of protecting hematopoietic tissues in vivo from the toxicity associated with radiation exposure. We report here the results of studies designed to further investigate the capability of various cytokines (IL-1 and interleukins-2 and -3) to protect bone marrow-derived hematopoietic progenitors [granulocyte-macrophage and megakaryocyte colony-forming units (CFU-GM and CFU-Meg)] from radiation exposure in vitro. Only IL-1 was effective in protecting CFU-GM and CFU-Meg from radiation-induced toxicity in the range of 1-10 U/ml; however, no protection was observed when the radiation dose was greater than 300 rad. The ability of IL-1 to block radiation-induced toxicity was negated in the presence of an antibody to IL-1. These studies provide further information on the effectiveness of IL-1 in protecting in vitro hematopoietic tissues from toxicity associated with radiation exposure.

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多种白细胞介素(IL-1、IL-2和IL-3)对骨髓祖细胞(CFU-GM和CFU-MEG)的体外放射保护作用
辐射暴露于各种系统可导致严重毒性的发展,称为急性辐射综合征,造血组织极易受到辐射引起的损伤。通常是造血毒性的程度决定了进一步肿瘤控制治疗剂量的可行性。因此,开发能够保护造血组织的药物具有重要的临床应用价值。细胞因子白细胞介素-1 (IL-1)已被证明是一种有效的药物,能够保护体内造血组织免受辐射暴露相关的毒性。我们在此报告了旨在进一步研究各种细胞因子(IL-1和白细胞介素-2和-3)在体外辐射照射下保护骨髓来源的造血祖细胞[粒细胞-巨噬细胞和巨核细胞集落形成单位(CFU-GM和CFU-Meg)]的能力的研究结果。在1 ~ 10 U/ml范围内,只有IL-1能有效保护CFU-GM和CFU-Meg的辐射毒性;然而,当辐射剂量大于300 rad时,没有观察到保护作用。IL-1阻断辐射诱导毒性的能力在IL-1抗体存在时被否定。这些研究为IL-1保护体外造血组织免受辐射相关毒性的有效性提供了进一步的信息。
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