Xie Cong-Hua, Zhang Ming-Sheng, Zhou Yun-Feng, Han Guang, Cao Zhen, Zhou Fu-Xiang, Zhang Gong, Luo Zhi-Guo, Wu Jian-Ping, Liu Hui, Chen Ji, Zhang Wen Jie
Department of Cancer Radio-Chemotherapy, Wuhan University Zhongnan Hospital and Cancer Research Center, Wuhan, Hubei 430071, P.R. China.
Oncol Rep. 2006 Jun;15(6):1429-36.
Radiotherapy of thoracic cancer often causes pulmonary inflammation leading to pneumonitis and fibrosis. We favor the hypothesis that cytokine-mediated multicellular interactions may result in the overexpression of proinflammatory cytokines such as TNF-alpha and TGF-beta1, which promotes progressive radiation-induced lung injury. The root of Angelica sinensis, known as 'Danggui' in Chinese medicine, is widely used to treat radiation-induced pneumonitis in humans and shows clinical efficacy and low/no toxicity with an unclear mechanism. Using quantitative RT-PCR and immunohistochemistry (IHC) methods, we investigated radiation-induced lung injury in a mouse model. C57BL/6 mice were assigned to 4 groups: no treatment (NT), Angelica Sinensis treatment only (AS), X-ray irradiation only (XRT, single fraction of 12 Gy irradiation to the thoraces) and AS treatment plus XRT (AS/XRT). Mice in NT and AS groups exhibited low TNF-alpha and TGF-beta1 mRNA levels and few positive cell counts for TNF-alpha (8-17 cells per field, x400 magnification) and TGF-beta1 (9-31 cells per field), respectively. In XRT mice, there were increased inflammatory cells positive for TNF-alpha and TGF-beta1 in lung tissue compared with NT mice (P<0.01). However, when XRT mice received AS treatment (AS/XRT), the number of inflammatory cells in lung tissue positive for both TNF-alpha and TGF-beta1 was decreased compared with XRT-only mice (P<0.01) accompanied by moderately decreased mRNA levels of TNF-alpha and TGF-beta1. We conclude that radiation induces expression of TNF-alpha and TGF-beta1 in the inflammatory cells of irradiated lung tissue during the pneumonic phase. The predominant localization of TNF-alpha and TGF-beta1 in inflammatory cell infiltrates suggests these cytokines' involvement in the process of radiation-induced pneumonitis. Moreover, effective down-regulation of TNF-alpha and TGF-beta1 in irradiated lung tissue by Angelica Sinensis is, at least in part, indicative of its clinical efficacy in treating radiation-induced pneumonitis.
胸段癌放疗常导致肺部炎症，进而引发肺炎和肺纤维化。我们支持这样一种假说，即细胞因子介导的多细胞相互作用可能导致促炎细胞因子如肿瘤坏死因子-α（TNF-α）和转化生长因子-β1（TGF-β1）的过度表达，从而促进放射性肺损伤的进展。当归的根，在中医里称为“当归”，被广泛用于治疗人类放射性肺炎，显示出临床疗效且毒性低/无毒性，但其作用机制尚不清楚。我们使用定量逆转录聚合酶链反应（RT-PCR）和免疫组织化学（IHC）方法，在小鼠模型中研究放射性肺损伤。将C57BL/6小鼠分为4组：未治疗组（NT）、仅当归治疗组（AS）、仅X射线照射组（XRT，单次12 Gy胸部照射）和当归治疗加XRT组（AS/XRT）。NT组和AS组小鼠的TNF-α和TGF-β1 mRNA水平较低，TNF-α（每视野8 - 17个细胞，×400放大倍数）和TGF-β1（每视野9 - 31个细胞）的阳性细胞计数也较少。与NT组小鼠相比，XRT组小鼠肺组织中TNF-α和TGF-β1阳性的炎性细胞增多（P<0.01）。然而，当XRT组小鼠接受当归治疗（AS/XRT）时，与仅接受XRT的小鼠相比，肺组织中TNF-α和TGF-β1阳性的炎性细胞数量减少（P<0.01），同时TNF-α和TGF-β1的mRNA水平适度降低。我们得出结论，在肺炎期，放疗诱导照射肺组织炎性细胞中TNF-α和TGF-β1的表达。TNF-α和TGF-β1在炎性细胞浸润中的主要定位表明这些细胞因子参与了放射性肺炎的发生过程。此外，当归对照射肺组织中TNF-α和TGF-β1的有效下调，至少部分表明其在治疗放射性肺炎方面具有临床疗效。
