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.