Azithromycin attenuates acute radiation-induced lung injury in mice

Radiation-induced lung injury (RILI) is a common and major obstacle in thoracic cancer radiotherapy, resulting in considerable morbidity and limiting the dose of radiation. However, an effective treatment option remains to be established. Therefore, the present study aimed to investigate the effects of azithromycin (AZM) in acute RILI with a mouse model. In the present study, C57BL/6 mice were given a single thoracic irradiation of 16 Gy and administered orally with AZM. The lung histopathological findings, the levels of malondialdehyde (MDA; an indicator of oxidative damage) and the concentration of pro-inflammatory and pro-fibrotic cytokines in plasma were assessed on 28 day following irradiation. In addition, the total cell counts in bronchoalveolar lavage fluid (BALF), the pro-inflammatory and pro-fibrotic cytokine gene expression in lung tissue were evaluated on day 7, 14 and 28 following irradiation. Administration with AZM markedly alleviated acute RILI as indicated by hematoxylin and eosin and Masson staining. The levels of MDA and total cell counts in BALF significantly reduced in AZM treated mice. AZM also down-regulated the concentration and mRNA expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α and transforming growth factor-β1. In addition, AZM attenuated the irradiation-induced increases in the mRNA expression of fibrotic markers (α-smooth muscle actin and α-1 type I collagen). AZM treatment mitigated the radiation-induced acute lung injury possibly by its anti-inflammatory and anti-fibrotic effects.