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Pneumonitis is a dose-limiting side effect of radiotherapy.  However, the underlying mechanisms of irradiation-induced pneumonitis are unclear.  Several observations suggest that the CD95/CD95-ligand (CD95L) system is involved in this process.  Therefore, we examined the development of pneumonitis in CD95- and CD95L-deficient and wild-type mice after single irradiation with 0 or 12.5 Gy by measuring breathing frequency, pulmonary resistance, and histopathologic changes.  Although wild-type mice developed pathognomonic alterations characteristic of pneumonitis (judged by alveolar wall...

Pneumonitis is a dose-limiting side effect of radiotherapy.  However, the underlying mechanisms of irradiation-induced pneumonitis are unclear.  Several observations suggest that the CD95/CD95-ligand (CD95L) system is involved in this process.  Therefore, we examined the development of pneumonitis in CD95- and CD95L-deficient and wild-type mice after single irradiation with 0 or 12.5 Gy by measuring breathing frequency, pulmonary resistance, and histopathologic changes.  Although wild-type mice developed pathognomonic alterations characteristic of pneumonitis (judged by alveolar wall thickness, interstitial edema, and interstitial and peribronchial inflammation) that paralleled increased breathing frequency ratio on days 5–70 (P<.03) with a maximum at day 37 (12.5 Gy, mean ratio = 1.05, 95% confidence interval [CI] = 1.01 to 1.08; P = .004 versus 0 Gy, mean ratio = 0.997, 95% CI = 0.976 to 1.02; P = .05) and pulmonary resistance (day 42, 12.5 Gy, mean = 0.51, 95% CI = 0.44 to 0.58 versus 0 Gy, mean = 0.40, 95% CI = 0.32 to 0.47; P = .03) after irradiation, no such changes were detected in CD95- or CD95L-deficient mice.  This report demonstrates for the first time, to our knowledge, that the CD95/CD95L system is important for the development of irradiation-induced pneumonitis.