Radiation produces differential changes in cytokine profiles in radiation lung fibrosis sensitive and resistant mice

Xiaoping Ao,David M Lubman,Mary A Davis,Theodore S Lawrence,Feng-Ming Kong,Lujun Zhao

doi:10.1186/1756-8722-2-6

Xiaoping Ao, David M Lubman + Show 4 more

Open Access

https://doi.org/10.1186/1756-8722-2-6

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Abstract

BackgroundRecent research has supported that a variety of cytokines play important roles during radiation-induced lung toxicity. The present study is designed to investigate the differences in early cytokine induction after radiation in sensitive (C57BL/6) and resistant mice (C3H).ResultsTwenty-two cytokines in the lung tissue homogenates, bronchial lavage (BAL) fluids, and serum from 3, 6, 12, 24 hrs to 1 week after 12 Gy whole lung irradiation were profiled using a microsphere-based multiplexed cytokine assay. The majority of cytokines had similar baseline levels in C57BL/6 and C3H mice, but differed significantly after radiation. Many, including granulocyte colony-stimulating factor (G-CSF), interleukin-6 (IL-6), and keratinocyte-derived chemokine (KC) were elevated significantly in specimens from both strains. They usually peaked at about 3–6 hrs in C57BL/6 and 6–12 hrs in C3H. At 6 hrs in lung tissue, G-CSF, IL-6, and KC increased 6, 8, and 11 fold in C57BL/6 mice, 4, 3, and 3 fold in the C3H mice, respectively. IL-6 was 10-fold higher at 6 hrs in the C57BL/6 BAL fluid than the C3H BAL fluid. MCP-1, IP-10, and IL-1α also showed some differences between strains in the lung tissue and/or serum. For the same cytokine and within the same strain of mice, there were significant linear correlations between lung tissue and BAL fluid levels (R2 ranged 0.46–0.99) and between serum and tissue (R2 ranged 0.56–0.98).ConclusionRadiation induced earlier and greater temporal changes in multiple cytokines in the pulmonary fibrosis sensitive mice. Positive correlation between serum and tissue levels suggests that blood may be used as a surrogate marker for tissue.

Highlights

Recent research has supported that a variety of cytokines play important roles during radiation-induced lung toxicity
Radiation-induced pulmonary injury to normal lung tissue is a dose-limiting complication for cancer patients receiving radiotherapy to the chest region [1,2,3]. Depending on both radiation dose and volume, lung injury is characterized by inflammation associated pneumonitis which may progress to permanent pulmonary fibrosis
Cytokine levels in lung tissue lysates We began by analyzing cytokine levels in the lungs of control mice

Summary

Introduction

Recent research has supported that a variety of cytokines play important roles during radiation-induced lung toxicity. Since a complex cytokine network initiates and sustains the inflammatory and fibrogenic processes associated with radiation-induced lung injury [9], the ability to simultaneously quantify multiple cytokines is critical for deciphering how they affect radiation-induced lung toxicity. One such assay, a microsphere-based sandwich immunoassay for flow cytometry, is a highly sensitive and selective multiplexed assay platform to simultaneously measure many cytokines in low volume samples, e.g. 25 μL sample for 22 mouse cytokines/chemokines [10]. This assay platform, the most comprehensive one available on the market during the time of our experiment, provides a powerful tool for multiple cytokine profiling and a more complete picture of the complex cytokine network

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