Elucidating the Mechanisms Behind Radiation Induced Pneumonitis and Pulmonary Fibrosis

Since adverse reactions in normal tissues after radiotherapy is a major dose-limiting factor, elucidation of the underlying molecular mechanisms is essential for improvement of radiotherapy. Radiation induced pneumonitis and consequential pulmonary fibrosis are well known as serious and frequent side effects after thoracic radiation therapy. Pneumonitis and consequential pulmonary fibrosis develop dose-dependently several months after irradiation, and their lethal potential impact affect the quality of life of the patients. Even though past clinical reports have indicated lower risk of advanced radiation therapies, especially carbon-ion radiotherapy, it is still an important issue for individual patients. Radiosensitivity varies depending on the genetic-background of individuals, and it is also associated with the severity of radiation-related adverse reactions. We aimed to identify molecular mechanisms, which can become novel targets for prevention or treatment of radiation induced pneumonitis and pulmonary fibrosis. To find biomarkers for prediction of prognosis or molecular targets for treatment of radiation pneumonitis/fibrosis, we performed histological analyses of the lung at different time points in fibrosis-prone (C57BL/6J) and fibrosis-resistant (C3H/He) mice strains and its F1 strain C3B6F1 mice after thoracic irradiation by carbon ion beam. In the mouse model, infiltration of inflammatory cells and mild fibrotic loci were observed in both mouse strains 24 weeks after 10Gy carbon ion irradiation. Interestingly, fibrotic loci developed and expanded, changing the shape of the lung in C57BL/6J mice, but not in C3H/He mice. Our recent analysis clearly highlighted that the type of infiltrated inflammatory cells including neutrophil and macrophage, and the difference in expression of lung remodeling proteins at these fibrotic loci, are critical factors in developing severe fibrosis after irradiation in a strain dependent manner.15th International Congress of Radiation Research (ICRR 2015