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 1-25Gy 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 10-25Gy 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.