Sequential radiation exposure: uncovering the potential of low dose ionizing radiation in mitigating high dose effects on immune cells

Abstract

Purpose

The radioadaptive response refers to a phenomenon wherein exposure to a low dose of ionizing radiation (LDIR) can induce a protective response in cells or organisms, reducing the adverse effects of a subsequent higher dose of ionizing radiation (HDIR). However, it is possible to administer the low dose after the challenge dose. This study was conducted to determine the potential mitigating effect of LDIR administered after HDIR on mice immune cells.

Materials and methods

Alongside the conventional adaptive response setting, one group of mice was initially exposed to HDIR and subsequently treated with LDIR. Neutrophil activation was done using DHR-reducing assay and cell proliferation was evaluated through CFSE-dilution assay in helper (CD4⁺) and cytotoxic (CD8⁺) T cells. Cytokine production by these T cell subsets was also assessed by intracellular staining using flow cytometry.

Results

The results of this study revealed no change in neutrophil function between any of the mice groups compared to the untreated control group. Although significant changes were not detected in the proliferation of CD4⁺ T cells, decreased proliferation was observed in stimulated CD8⁺ T cells in the HDIR group. In contrast to IFN-ɣ, which showed no evident change in either of the T cell subsets after stimulation, IL-4 was rigorously dropped in stimulated CD4⁺ T cells in the HDIR group.

Conclusions

In summary, the results of this study indicated that the administration of LDIR to mice before HDIR was not able to reduce the detrimental effects of HDIR in our experimental setting. Instead, we observed a mitigating effect of LDIR when administered after the challenge dose. This suggests that not only the dose and duration but also the order of LDIR relative to HDIR affects its efficacy.

Keywords:

• Ionizing radiation
• adaptive response
• mitigating effect
• neutrophil
• T cell
• cytokine

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was performed in partial fulfillment of the requirements for the PhD by Research degree from the Ionizing and Non-Ionizing Radiation Protection Research Center (INIRPRC) affiliated to Shiraz University of Medical Sciences (SUMS) awarded to Sadegh Masoudi. This work received financial support from a grant (grant number: 16317) provided by Shiraz University of Medical Sciences.

Notes on contributors

Sadegh Masoudi

Sadegh Masoudi is a PhD research student at the Ionizing and Non-Ionizing Radiation Protection Research Center (INIRPRC), School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

Mehdi Kalani

Mehdi Kalani is an Assistant Professor of Immunology at the Professor Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. He has published more than 60 research articles in leading international and national journals.

Ali Alavianmehr

Ali Alavianmehr is a PhD student of Medical Immunology at the Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. He has published about 6 research articles in the field of immunology.

Mohammad Amin Mosleh-Shirazi

Mohammad Amin Mosleh-Shirazi is an Associate Professor of Medical Physics at the Ionizing and Non-Ionizing Radiation Protection Research Center (INIRPRC), School of Paramedical Sciences, and Radiotherapy Department and Center for Research in Medical Physics and Biomedical Engineering, Shiraz University of Medical Sciences, Shiraz, Iran. He has published more than 100 research articles in the field of radiation research.

Seyed Mohammad Javad Mortazavi

Seyed Mohammad Javad Mortazavi is a Professor of Medical Physics at the Ionizing and Non-Ionizing Radiation Protection Research Center (INIRPRC), School of Paramedical Sciences, and Department of Medical Physics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. He has published more than 600 research articles in the field of radiation protection.

Shirin Farjadian

Shirin Farjadian is a Professor of Immunology at the Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. She has great research experience in different aspects of immunology, especially immunogenetics. She has published more than 100 research articles in leading international and national journals.