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An experimental model-based exploration of cytokines in ablative radiation-induced lung injury in vivo and in vitro

 Zhen-Yu Hong  ;  Kwang Hyun Song  ;  Joo-Heon Yoon  ;  Jaeho Cho  ;  Michael D. Story 
 LUNG, Vol.193(3) : 409-419, 2015 
Journal Title
Issue Date
Ablation Techniques* ; Alveolar Epithelial Cells/immunology ; Alveolar Epithelial Cells/metabolism ; Alveolar Epithelial Cells/radiation effects ; Animals ; Coculture Techniques ; Cytokines/blood* ; Cytokines/genetics ; Cytokines/immunology ; Disease Models, Animal ; Fibroblasts/immunology ; Fibroblasts/metabolism ; Fibroblasts/radiation effects ; Gene Expression Regulation ; Lung/immunology ; Lung/metabolism ; Lung/radiation effects* ; Macrophages, Alveolar/immunology ; Macrophages, Alveolar/metabolism ; Macrophages, Alveolar/radiation effects ; Mice ; Mice, Inbred C3H ; NIH 3T3 Cells ; Radiation Dosage ; Radiation Pneumonitis/blood* ; Radiation Pneumonitis/etiology ; Radiation Pneumonitis/genetics ; Radiation Pneumonitis/immunology ; Radiosurgery* ; Time Factors
Stereotactic ablative radiotherapy ; Cytokine ; Radiation pneumonitis ; Radiation fibrosis ; Small-animal model
INTRODUCTION: 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.
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1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Yoon, Joo Heon(윤주헌)
Cho, Jae Ho(조재호) ORCID logo https://orcid.org/0000-0001-9966-5157
Hong, Zhen-Yu(홍진우)
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