Wang Bao-Zhong, Wang Li-Ping, Han Hui, Cao Fang-Li, Li Guang-Yao, Xu Jun-Long, Wang Xiu-Wen, Wang Le-Xin
1Department of Oncology, Qilu Hospital, Shandong University, Jinan, P. R. China.
Exp Lung Res. 2014 Mar;40(2):77-85. doi: 10.3109/01902148.2013.872210. Epub 2014 Jan 21.
To investigate the effect of interleukin-17A (IL-17A) antibodies on radiation-induced lung injuries in mice.
The thorax of 135 mice were divided into Sham (n = 30), radiation control (RC, n = 35), treatment (n = 35, IL-17A-neutralizing antibody, 4 μg/mouse, IV, 4 days per month for 4 months) and placebo group (n = 35) before a single dose irradiation (15 Gy) to the thorax. Inflammation and collagen contents in the lung tissues were examined, and the concentration of IL-17A, TGF-β1, and IL-6 in bronchoalveolar lavage fluid (BALF) were measured. In another 50 animals, 180-day survival rate following the irradiation and treatment was calculated by Kaplan-Meier method.
Sixteen weeks after the irradiation and treatment, there was significant inflammatory cell infiltration and interstitial collagen depositions in the radiation control and placebo groups, whereas these changes were relatively mild in the treatment group. The percentage of grade II and III alveolitis in the treatment group (16%, P < .05) was lower than in the RC (72%) or placebo group (64%). The mean Aschcroft fibrosis scores were 2.8 (treatment group), 5.2 (RC), and 4.8 (placebo group), respectively. The scores of treatment group was lower than that of RC (P < .001) or placebo group (P < .001). The IL-17A, TGF-β, and IL-6 concentrations in the treatment group were lower than in the RC and placebo group (P < .01) following the irradiation. The 180-day mortality rate in the treatment group was lower than in the RC group 16.7% versus 75.0%, P < .05).
IL-17A antibody treatment alleviates radiation-induced pneumonitis and subsequent fibrosis, and improvise postirradiation survival.
研究白细胞介素-17A（IL-17A）抗体对小鼠放射性肺损伤的影响。
将135只小鼠的胸部在单次胸部照射（15 Gy）前分为假手术组（n = 30）、辐射对照组（RC，n = 35）、治疗组（n = 35，IL-17A中和抗体，4 μg/小鼠，静脉注射，每月4天，共4个月）和安慰剂组（n = 35）。检测肺组织中的炎症和胶原含量，并测定支气管肺泡灌洗液（BALF）中IL-17A、转化生长因子-β1（TGF-β1）和白细胞介素-6（IL-6）的浓度。在另外50只动物中，采用Kaplan-Meier法计算照射和治疗后的180天生存率。
照射和治疗16周后，辐射对照组和安慰剂组出现明显的炎症细胞浸润和间质胶原沉积，而治疗组的这些变化相对较轻。治疗组Ⅱ级和Ⅲ级肺泡炎的百分比（16%，P < 0.05）低于辐射对照组（72%）或安慰剂组（64%）。平均阿什克罗夫特纤维化评分分别为2.8（治疗组）、5.2（辐射对照组）和4.8（安慰剂组）。治疗组的评分低于辐射对照组（P < 0.001）或安慰剂组（P < 0.001）。照射后治疗组的IL-17A、TGF-β和IL-6浓度低于辐射对照组和安慰剂组（P < 0.01）。治疗组的180天死亡率低于辐射对照组（16.7%对75.0%，P < 0.05）。
IL-17A抗体治疗可减轻放射性肺炎及随后的纤维化，并提高照射后的生存率。
