Inflammatory cytokines have been suggested to play important roles in radiation-induced lung injury (RILI). Identifying significantly changed circulating and tissue cytokines after thoracic irradiation will aid in deciphering the mechanism of RILI and identifying potential biomarkers to predict clinical outcome. Herein, the levels of 24 cytokines were measured in serial plasma samples and lung tissue samples collected from a pilot study where nonhuman primates (NHPs) received 11.5 Gy whole thoracic lung irradiation (WTLI) and were then treated with or without a medical countermeasure, AEOL 10150 [a superoxide dismutase (SOD) mimetic]. Seven plasma cytokines (i.e., IP-10, MCP-1, IL-12, IL-15, IL-16, IL-7 and IL-6) were found to be significantly changed at different time points due to WTLI. Plasma IP-10 and MDC were significantly changed between the vehicle group and the drug group. The levels of IP-10, MCP-1, MIP-1α, TARC, IL-17, TNF-β and IL-6 were significantly elevated in the lung tissue lysates of NHPs that received WTLI versus radiation-naïve NHPs. The terminal plasma concentrations of IP-10, MDC, TARC, IL-12, IL-15 and IL-6 were significantly correlated with their levels in the lung tissue. The levels of four cytokines (MCP-4, IL-17, TNF-β and IL-2) at early time points (≤8 weeks postirradiation) were significantly correlated with their terminal plasma levels, respectively. Statistical analysis indicated that circulating cytokines could be discriminatory predictors of AEOL 10150 treatment. Taken together, our data suggested that the cytokine profiles were significantly changed after WTLI as well as mitigator treatment, and that the plasma cytokine profiles could potentially be used to distinguish vehicle or mitigator treatment after WTLI in a NHP model.

中文翻译：

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在非人类灵长类动物模型中识别与胸腔照射和AEOL 10150治疗相关的循环和肺组织细胞因子。

炎症细胞因子已被认为在放射性肺损伤（RILI）中起重要作用。识别胸腔照射后循环和组织细胞因子的显着变化将有助于破译RILI的机制，并识别潜在的生物标志物以预测临床结果。在本文中，从先驱研究中收集的一系列血浆样品和肺组织样品中测量了24种细胞因子的水平，在该研究中，非人类灵长类动物（NHP）接受了11.5 Gy全胸肺照射（WTLI），然后接受或不采用医学对策AEOL进行治疗10150 [超氧化物歧化酶（SOD）模拟物]。发现七种血浆细胞因子（即IP-10，MCP-1，IL-12，IL-15，IL-16，IL-7和IL-6）在不同时间点由于WTLI而发生了显着变化。在载体组和药物组之间，血浆IP-10和MDC发生了显着变化。与未接受过辐射的NHP相比，接受WTLI的NHP的肺组织裂解物中IP-10，MCP-1，MIP-1α，TARC，IL-17，TNF-β和IL-6的水平显着升高。IP-10，MDC，TARC，IL-12，IL-15和IL-6的终末血浆浓度与其在肺组织中的水平显着相关。早期（照射后≤8周）四种细胞因子（MCP-4，IL-17，TNF-β和IL-2）的水平分别与它们的终末血浆水平显着相关。统计分析表明，循环细胞因子可能是AEOL 10150治疗的判别指标。综上所述，我们的数据表明，WTLI和缓解剂治疗后，细胞因子谱发生了显着变化，