Role of type II pneumocytes in pathogenesis of radiation pneumonitis: dose response of radiation-induced lung changes in the transient high vascular permeability period

Abstract

We studied the dose response of pulmonary changes at 3 weeks after 1–25 Gy irradiation and we investigated the effects of an anti-inflammatory drug. Wistar rats were given a single dose of 1–25 Gy irradiation to the thorax. Group one was treated with saline only, while group two was administered subcutaneously a combination of pentoxifylline (35 mg/kg) and dexamethasone (1 mg/kg) twice per week. Lungs were examined histochemically and number of neutrophile granulocytes, alveolar septal thickness, air/tissue ratio, number of alveoli per field, number of type II pneumocytes per alveolus, and occludin 1 expression were measured. A significant dose-dependent depletion of type II pneumocytes was found after irradiation with a dose of 1 Gy and higher. Alveolar neutrophils increased after 1 Gy with a dose dependency noted after 10–25 Gy and alveolar septa thickening followed 5–25 Gy. A lower occludin 1 expression was observed in animals irradiated with the doses of 5–20 Gy, indicating an effect on vascular permeability. Anti-inflammatory therapy partially inhibited the increase of neutrophils at all radiation doses and the depletion of type II pneumocytes after doses of 1, 10, and 15 Gy. Occludin 1 did not decrease in the lungs of rats treated with the anti-inflammatory drugs as it did in most rats treated only with saline. Our results suggest that pneumocytes depletion is a major factor responsible for radiation pneumonitis development and that these changes may be compensated for provided radiation doses are below the threshold.