Research Division for Radiation Science, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea.
Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul, Republic of Korea.
Front Immunol. 2023 May 25;14:1182927. doi: 10.3389/fimmu.2023.1182927. eCollection 2023.
Low-dose radiation therapy (LDRT) can suppress intractable inflammation, such as that in rheumatoid arthritis, and is used for treating more than 10,000 rheumatoid arthritis patients annually in Europe. Several recent clinical trials have reported that LDRT can effectively reduce the severity of coronavirus disease (COVID-19) and other cases of viral pneumonia. However, the therapeutic mechanism of LDRT remains unelucidated. Therefore, in the current study, we aimed to investigate the molecular mechanism underlying immunological alterations in influenza pneumonia after LDRT. Mice were irradiated to the whole lung 1 day post-infection. The changes in levels of inflammatory mediators (cytokines and chemokines) and immune cell populations in the bronchoalveolar lavage (BALF), lungs, and serum were examined. LDRT-treated mice displayed markedly increased survival rates and reduced lung edema and airway and vascular inflammation in the lung; however, the viral titers in the lungs were unaffected. Levels of primary inflammatory cytokines were reduced after LDRT, and transforming growth factor-β (TGF-β) levels increased significantly on day 1 following LDRT. Levels of chemokines increased from day 3 following LDRT. Additionally, M2 macrophage polarization or recruitment was increased following LDRT. We found that LDRT-induced TGF-β reduced the levels of cytokines and polarized M2 cells and blocked immune cell infiltration, including neutrophils, in BALF. LDRT-induced early TGF-β production was shown to be a key regulator involved in broad-spectrum anti-inflammatory activity in virus-infected lungs. Therefore, LDRT or TGF-β may be an alternative therapy for viral pneumonia.
低剂量辐射疗法（LDRT）可以抑制类风湿关节炎等难治性炎症，并且每年在欧洲用于治疗超过 10000 例类风湿关节炎患者。最近的几项临床试验报告称，LDRT 可以有效减轻冠状病毒病（COVID-19）和其他病毒性肺炎的严重程度。然而，LDRT 的治疗机制仍不清楚。因此，在当前研究中，我们旨在研究 LDRT 后流感肺炎免疫改变的分子机制。小鼠在感染后 1 天对全肺进行照射。检测支气管肺泡灌洗液（BALF）、肺和血清中炎症介质（细胞因子和趋化因子）和免疫细胞群的变化。LDRT 治疗的小鼠显示出明显提高的存活率，以及减轻的肺水肿和气道及血管炎症，但肺部的病毒滴度不受影响。LDRT 后初级炎症细胞因子水平降低，转化生长因子-β（TGF-β）水平在 LDRT 后第 1 天显著增加。趋化因子水平从 LDRT 后第 3 天开始增加。此外，LDRT 后 M2 巨噬细胞极化或募集增加。我们发现，LDRT 诱导的 TGF-β降低了细胞因子水平并极化了 M2 细胞，并阻止了包括中性粒细胞在内的免疫细胞在 BALF 中的浸润。LDRT 诱导的早期 TGF-β产生是参与病毒感染肺中广谱抗炎活性的关键调节剂。因此，LDRT 或 TGF-β可能是病毒性肺炎的替代疗法。
