Effect of total body irradiation on late lung effects: Hidden dangers

Abstract

Purpose: In our ongoing investigation into the consequences of a radiological terrorism or nuclear dispersion event, we assessed whether a dose range that is believed to be sub-threshold for the development of lung endpoints results in late pathological changes and, secondarily, whether those late changes affect the lung's ability to respond to subsequent challenge.

Materials and methods: C57BL/6J mice received total body irradiation (0.5–10 Gy) and were followed for 6–18 months after irradiation. At 12 and 15 months, a subset of mice was exposed to a second challenge (aerosolised lipopolysaccharide [LPS]).

Results: Cytokines shown to be upregulated early (hours) following irradiation (interleukin [IL]6, keratinocyte chemoattractant [KC], IL1B, and IL1R2) demonstrated increases in messenger ribose nucleic acid (mRNA) expression at late time points, beginning at nine months. Although persistent, dose-dependent increases in T cell counts were seen, no other overt changes in pathophysiology were observed. Nonetheless, animals that were exposed to a secondary challenge at late time points demonstrated an increased inflammatory cell recruitment and persistence in response relative to controls.

Conclusions: We propose that, following doses that elicit little change in pathophysiology, sub-clinical radiation-induced injury increases the lungs' susceptibility to a secondary challenge, possibly through a radiation-induced alteration in the immune defense system.

Keywords:

• lung late effects
• secondary challenge
• late cytokine expression

Acknowledgements

We would like to thank Dr Bruce Fenton and Mr Scott Paoni for their assistance with the image analysis and Ms Amy Huser for her editorial and research assistance with this manuscript. This work was supported by both the Centers for Medical Countermeasures against Radiation Program, National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) U19-AI067733 and U19-AI091036, and National Institute of Environmental Health Sciences (NIEHS)/Environmental Health Sciences (EHS) P30 ES01247.

Declaration of interest:

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.