Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Int J Radiat Oncol Biol Phys. 2019 Mar 1;103(3):719-727. doi: 10.1016/j.ijrobp.2018.10.007. Epub 2018 Oct 15.
To evaluate the acute changes in leukocyte populations after focal irradiation and to assess the role of interleukin 6 (IL-6) in acute and late radiation injury.
Mice were surgically implanted with a radiopaque marker on the surface of the small intestine. Mice were then imaged with cone beam computed tomography to locate the marker and irradiated with 18 Gy of 5 × 5 mm collimated x-rays onto the marked intestine using the Small Animal Radiation Research Platform. Intestinal sections and blood were harvested 1, 3.5, 7, and 14 days and 2 months postirradiation (post-IR) for histology and complete blood count, respectively. Immune cell populations were assessed by immunofluorescence in the acute phase. Collagen deposition was assessed 2 months post-IR. IL-6 intestinal sections were assessed post-IR for morphology, EdU, Ki67, and TUNEL in comparison to IL-6 mice. Furthermore, a set of IL-6 mice were treated with anti-IL-6R to assess the role of IL-6 in late intestinal injury.
Intestinal radiation damage peaked 14 days post-IR, and fibrosis had developed by 60 days post-IR. There was a marked infiltration of immune cells into the irradiated intestine, with increased neutrophils, macrophages, B-cells, and CD4 T cells maintained from 3.5 to 14 days post-IR. CD8 T cells were decreased from days 7 to 14 post-IR. Systemically, leukocytes were increased in the peripheral blood 14 days post-IR with anemia being maintained from 14 days to 2 months. IL-6 was significantly increased in the serum post-IR. IL-6 mice demonstrated worsened intestinal injury acutely post-IR. Moreover, anti-IL-6R-treated mice presented with worsened intestinal fibrosis 2 months post-IR.
Focal irradiation of the intestine produced a significant increase in immune cells in the irradiated area and systemic inflammation and anemia. Blockade of IL-6 signaling was found to exacerbate acute intestinal injury and late intestinal injury after focal irradiation.
评估局部照射后白细胞群的急性变化，并评估白细胞介素 6（IL-6）在急性和晚期辐射损伤中的作用。
将放射性标记物通过手术植入小鼠小肠表面。然后使用锥形束 CT 对小鼠进行成像，以找到标记物，并使用小动物辐射研究平台将 5×5mm 准直 X 射线照射到标记的小肠上，剂量为 18Gy。照射后 1、3.5、7 和 14 天和 2 个月，分别采集肠组织和血液，用于组织学和全血细胞计数。在急性期通过免疫荧光评估免疫细胞群。照射后 2 个月评估胶原沉积。与 IL-6 小鼠相比，评估 IL-6 肠组织的形态、EdU、Ki67 和 TUNEL。此外，一组 IL-6 小鼠用抗 IL-6R 治疗，以评估 IL-6 在晚期肠道损伤中的作用。
肠道辐射损伤在照射后 14 天达到高峰，照射后 60 天出现纤维化。照射的小肠有明显的免疫细胞浸润，中性粒细胞、巨噬细胞、B 细胞和 CD4 T 细胞从照射后 3.5 天到 14 天持续增加。CD8 T 细胞从第 7 天到第 14 天减少。外周血白细胞在照射后 14 天增加，贫血从 14 天持续到 2 个月。照射后血清中 IL-6 明显增加。IL-6 小鼠在照射后急性肠道损伤加重。此外，抗 IL-6R 治疗的小鼠在照射后 2 个月出现更严重的肠道纤维化。
小肠局部照射会导致照射区域和全身炎症及贫血的免疫细胞显著增加。阻断 IL-6 信号传导被发现会加重局部照射后的急性肠道损伤和晚期肠道损伤。
