Abstract
BackgroundThe lung response to radiation exposure can involve an immediate or early reaction to the radiation challenge, including cell death and an initial immune reaction, and can be followed by a tissue injury response, of pneumonitis or fibrosis, to this acute reaction. Herein, we aimed to determine whether markers of the initial immune response, measured within days of radiation exposure, are correlated with the lung tissue injury responses occurring weeks later.MethodsInbred strains of mice known to be susceptible (KK/HIJ, C57BL/6J, 129S1/SvImJ) or resistant (C3H/HeJ, A/J, AKR/J) to radiation-induced pulmonary fibrosis and to vary in time to onset of respiratory distress post thoracic irradiation (from 10–23 weeks) were studied. Mice were untreated (controls) or received 18 Gy whole thorax irradiation and were euthanized at 6 h, 1d or 7 d after radiation treatment. Pulmonary CD4+ lymphocytes, bronchoalveolar cell profile & cytokine level, and serum cytokine levels were assayed.ResultsThoracic irradiation and inbred strain background significantly affected the numbers of CD4+ cells in the lungs and the bronchoalveolar lavage cell differential of exposed mice. At the 7 day timepoint greater numbers of pulmonary Th1 and Th17 lymphocytes and reduced lavage interleukin17 and interferonγ levels were significant predictors of late stage fibrosis. Lavage levels of interleukin-10, measured at the 7 day timepoint, were inversely correlated with fibrosis score (R = −0.80, p = 0.05), while serum levels of interleukin-17 in control mice significantly correlated with post irradiation survival time (R = 0.81, p = 0.04). Lavage macrophage, lymphocyte or neutrophil counts were not significantly correlated with either of fibrosis score or time to respiratory distress in the six mouse strains.ConclusionSpecific cytokine and lymphocyte levels, but not strain dependent lavage cell profiles, were predictive of later radiation-induced lung injury in this panel of inbred strains.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-015-0359-y) contains supplementary material, which is available to authorized users.
Highlights
The radiation-induced lung injury is thought to occur through the ionizing radiation producing reactive oxygen species which induce lesions in DNA leading to damage of the alveolar epithelium [1] and capillary endothelium [2]
Initial radiation response assays such as chromosomal aberrations, DNA damage and cell survival in cultured fibroblasts or lymphocytes offered conflicting results between in vitro cellular radiosensitivity and in vivo normal tissue response [9,10,11,12] suggesting that intrinsic radiosensitivity at the cellular level is not the only determinant for radiotherapy side-effects
In this study we characterised the primary radiation injury response of the lung following thoracic irradiation in six inbred mouse strains in terms of infiltrating Thelper lymphocyte populations, bronchoalveolar lavage cell differentials, as well as serum and lavage cytokine measurements, and investigated whether any of these initial immune response markers predicted for the late disease phenotypes in the lung
Summary
The radiation-induced lung injury is thought to occur through the ionizing radiation producing reactive oxygen species which induce lesions in DNA leading to damage of the alveolar epithelium [1] and capillary endothelium [2]. Paun et al Radiation Oncology (2015) 10:45 continuum of cytokine-based, multicellular interactions [13] This has prompted the study of early circulatory markers as predictive assays and has revealed associations of serum interleukins (Il6, Il1a, Il8, Il10) with pneumonitis [14,15,16,17]. None of these markers, robustly correlates with late tissue injury supporting the notion that the late stage response is dictated by a complex cytokine cascade which develops following the initial injury [18,19]. We aimed to determine whether markers of the initial immune response, measured within days of radiation exposure, are correlated with the lung tissue injury responses occurring weeks later
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
