Study to control radiation lung damages.

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Because side effects of lung irradiation, such as lung fibrosis and radiation pneumonitis, occur 6-12 months after irradiation, long experiment period is required for investigation on such side effects using mice or rats.We investigated effects of Argatroban on lung fibrosis after irradiation. Right lungs of rats were exposed to 17 Gy electron radiation with or without treatment with Argatroban. In the group of rats treated with Argatroban, lung fibrosis was not severe and the numbers of phagocytes invading into the lungs were significantly less compared with those in the non-treated group of rats.Radiation pneumonitis is usually observed in the irradiated area. However, it has been reported that it sometimes occurs outside the irradiated area. This suggests that not only radiation-induced damage but also the reaction of the irradiated host may cause radiation pneumonitis. Furthermore, radiation pneumonitis was not observed in the intercellular adhesion molecule 1 (ICAM-1) knockout mice, which suggests the involvement of immune response of the irradiated host to radiation pneumonitis. To investigate the role of macrophages in the development of pneumonitis, we investigated the response of macrophages to ionizing radiation in vitro. Significant increases of IL-1 β and IL-6 mRNA were observed 1-2 hours after irradiation, and significant decreases of these mRNA were observed 4 hours after irradiation. We will investigate (1) the expression of TNF- α in macrophages, which is reported to be important for tissue damage, and (2) the protective effects of HGF and Argatroban against lung damage.