Journal Article

Irradiation-Induced Pneumonitis Mediated by the CD95/CD95-Ligand System

Frank Heinzelmann, Verena Jendrossek, Kirsten Lauber, Kerstin Nowak, Therese Eldh, Ruzica Boras, Rene Handrick, Marco Henkel, Christian Martin, Stefan Uhlig, David Köhler, Holger K. Eltzschig, Manfred Wehrmann, Wilfried Budach and Claus Belka

in JNCI: Journal of the National Cancer Institute

Volume 98, issue 17, pages 1248-1251
Published in print September 2006 | ISSN: 0027-8874
Published online September 2006 | e-ISSN: 1460-2105 | DOI:

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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 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.

Journal Article.  3244 words.  Illustrated.

Subjects: Medical Oncology

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