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JNCI Journal of the National Cancer Institute 2006 98(17):1248-1251; doi:10.1093/jnci/djj335
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© 2006 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

BRIEF COMMUNICATION

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, Claus Belka

Affiliations of authors: Departments of Radiation Oncology (FH, VJ, KN, TE, RB, RH, MH, CB), Internal Medicine I (KL), Anesthesiology and Intensive Care Medicine (DK, HKE), and Pathology (MW), University of Tuebingen, Tuebingen, Germany; Department of Radiation Oncology, University of Duesseldorf, Duesseldorf, Germany (WB); Department of Pulmonary Pharmacology, Research Center Borstel, Leibniz Center for Medicine and Bioscience, Borstel, Germany (CM, SU); Institute of Pharmacology and Toxicology, Aachen, Germany (SU)

Correspondence to: Claus Belka, MD, Department of Radiation Oncology, University of Tuebingen, Hoppe-Seyler-Str. 3, D-72076 Tuebingen, Germany (e-mail: claus.belka{at}uni-tuebingen.de).

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.


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