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An Experimental Model-Based Exploration of Cytokines in Ablative Radiation-Induced Lung Injury In Vivo and In Vitro

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Abstract

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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Acknowledgments

This work was supported by the Nuclear Research and Development Program (NRF-2011-0031695)(JC) and the Radiation Technology R&D program (NRF-2013M2A2A7042978) (JC) through the National Research Foundation of Korea, funded by the Ministry of Science, ICT, and Future Planning; by a faculty research grant from the Yonsei University College of Medicine for 2014 (6-2014-0031)(JC); and by a grant from the Varian Corporation (MDS).

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea

    Zhen-Yu Hong & Jaeho Cho

  2. Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2201 Inwood Rd, Dallas, TX, 75093, USA

    Kwang Hyun Song & Michael D. Story

  3. Department of Otorhinolaryngology, BK 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea

    Joo-Heon Yoon

  4. Department of Medical Oncology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan Province, China

    Zhen-Yu Hong

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  1. Zhen-Yu Hong
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Correspondence to Jaeho Cho or Michael D. Story.

Additional information

The authors dedicate this article to the late Dr. Reinhard Kodym.

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Hong, ZY., Song, K.H., Yoon, JH. et al. An Experimental Model-Based Exploration of Cytokines in Ablative Radiation-Induced Lung Injury In Vivo and In Vitro. Lung 193, 409–419 (2015). https://doi.org/10.1007/s00408-015-9705-y

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  • DOI: https://doi.org/10.1007/s00408-015-9705-y

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