An experimental model-based exploration of cytokines in ablative radiation-induced lung injury in vivo and in vitro.
BACKGROUND
Stereotactic ablative radiotherapy is a newly emerging radiotherapy treatment method that, compared with conventionally fractionated radiation therapy (CFRT), allows an ablative dose of radiation to be delivered to a confined area around a tumor. The aim of the present study was to investigate the changes of various cytokines that may be involved in ablative radiation-induced lung injury in vitro and in vivo.


METHODS
In the in vivo study, ablative-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal irradiator. The levels of 24 cytokines in the peripheral blood were tested at several time points after irradiation. For the in vitro study, three mouse cell types (type II pneumocytes, alveolar macrophages, and fibroblasts) known to play important roles in radiation-induced pneumonitis and lung fibrosis were analyzed using a co-culture system.


RESULTS
In the in vivo study, we found obvious patterns of serum cytokine changes depending on the volume of tissue irradiated (2-mm vs. 3.5-mm collimator). Only the levels of 3 cytokines increased with the 2-mm collimator at the acute phase (1-2 weeks after irradiation), while the majority of cytokines were elevated with the 3.5-mm collimator. In the in vitro co-culture system, after the cells were given an ablative dose of irradiation, the levels of five cytokines (GM-CSF, G-CSF, IL-6, MCP-1, and KC) increased significantly in a dose-dependent manner.


CONCLUSIONS
The cytokine levels in our radiation-induced lung injury model showed specific changes, both in vivo and in vitro. These results imply that biological studies related to ablative-dose small-volume irradiation should be investigated using the corresponding experimental models rather than on those simulating large-volume CFRT.
Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
Zhen-Yu
ZY
Hong
Kwang Hyun
KH
Song
Joo-Heon
JH
Yoon
Jaeho
J
Cho
Michael D
MD
Story
D055011:Ablation Techniques; D056809:Alveolar Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D000818:Animals; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D041681:NIH 3T3 Cells; D011829:Radiation Dosage; D017564:Radiation Pneumonitis / Q000097:blood* / Q000209:etiology / Q000235:genetics / Q000276:immunology; D016634:Radiosurgery; D013997:Time Factors
D016207:Cytokines