Irradiation induces a biphasic expression of pro-inflammatory cytokines in the lung.
OBJECTIVE
The precise pathophysiological mechanisms of radiation-induced lung injury are poorly understood, but have been shown to correlate with dysregulation of different cytokines. The purpose of this study was to evaluate the time course of the pro-inflammatory cytokines tumor necrosis factor-(TNF-)alpha, interleukin-(IL-)1alpha and IL-6 after whole-lung irradiation.


METHODS
The thoraces of C57BL/6J mice were irradiated with 12 Gy. Treated and control mice were sacrificed at 0.5, 1, 3, 6, 12, 24, 48, 72 h, 1, 2, 4, 8, 16, and 24 weeks post irradiation (p. i.). Real-time multiplex RT-PCR (reverse transcriptase polmyerase chain reaction) was established to evaluate the expression of TNF-alpha, IL-1alpha and IL-6 in the lung tissue of the mice. For histological analysis, lung tissue sections were stained by hematoxylin and eosin.


RESULTS
Multiplex RT-PCR analysis revealed a biphasic expression of these pro-inflammatory cytokines in the lung tissue after irradiation. After an initial increase at 1 h p. i. for TNF-alpha and at 6 h p. i. for IL-1alpha and IL-6, the mRNA expression of these pro-inflammatory cytokines returned to basal levels (48 h, 72 h, 1 week, 2 weeks p. i.). During the pneumonic phase, TNF-alpha, IL-1alpha and IL-6 were significantly elevated and revealed their maximum at 8 weeks p. i. Histopathologic evaluation of the lung sections obtained within 4 weeks p. i. revealed only minor lung damage in 5-30% of the lung tissue. By contrast, at 8, 16, and 24 weeks p. i., 70-90% of the lung tissue revealed histopathologically detectable organizing alveolitis.


CONCLUSIONS
Irradiation induces a biphasic expression of pro-inflammatory cytokines in the lung. The initial transitory cytokine response occurred within the first hours after lung irradiation with no detectable histopathologic alterations. The second, more persistent cytokine elevation coincided with the onset of histologically discernible organizing acute pneumonitis.
Rübe
Claudia E
CE
Department of Radiotherapy-Radiooncology, Saarland University, Homburg/Saar, Germany. claudia.ruebe@uniklinik-saarland.de
Wilfert
Falk
F
Palm
Jan
J
König
Jochem
J
Burdak-Rothkamm
Susanne
S
Liu
Li
L
Schuck
Andreas
A
Willich
Normann
N
Rübe
Christian
C
D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics* / Q000528:radiation effects; D017931:DNA Primers; D005260:Female; D007249:Inflammation / Q000503:physiopathology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D017931:DNA Primers