Involvement of bystander effect in suppression of the cytokine production induced by heavy-ion broad beams

Abstract

Purpose: Immune cells accumulate in and around cancers and cooperate with each other using specific cytokines to attack the cancer cells. The heavy-ion beams for cancer therapy may stimulate immune cells and affect on the immune system. However, it is still poorly understood how the immune cells are stimulated by ion-beams. Here, we irradiated immune cells using heavy-ion beams and analyzed changes in production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) that are important cytokine for the cancer treatment.

Materials and methods: The human THP-1 monocytes were differentiated into macrophages and then irradiated using carbon-ion broad-beams (108 keV μm⁻¹). To examine the bystander response after heavy-ion irradiation, a very small fraction (approx. 0.45%) of the cell population was irradiated using heavy-ion microbeams. After irradiation, we examined the cytokine productions.

Results: When cells were irradiated with 5 Gy, cytokine levels were reduced after both microbeam irradiation and broad-beam irradiation. TNF-α production of macrophages with the nitric oxide (NO) inhibitor-treatment increased after carbon-ion broad-beam. NO was involved in the radiation-induced suppression of TNF-α production.

Conclusions: The suppression of cytokine production arose after irradiation with heavy-ions, and may also be induced in the surrounding non-irradiated cells via the bystander effect.

Keywords::

• Heavy-ion
• bystander effect
• tumor necrosis factor-α
• interleukin-6
• nitric oxide

Acknowledgements

The authors are grateful to Dr Yutaka Oono, Dr Hideki Matsumoto, and Dr Masanori Tomita for technical support. We also thank members of the Microbeam Radiation Biology Group at the JAEA for providing useful advice and cooperation. This work was also supported by the staff at the TIARA of JAEA.

Declaration of interest

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