Ionizing radiation-induced macrophage activation: augmentation of nitric oxide production and its significance.

Radiation is an important therapy for many kinds of cancer. However, it can result in the inflammation and accompanying injury. Recently, it is being recognized that the nitric oxide (NO) produced in macrophages activated by ionizing radiation is an important mediator. Ionizing radiation has been confirmed to potentiate NO production in macrophages, though the mechanism is not clear. We have shown that the increase of NO production in irradiated macrophages contributed to tumoricidal activity, with the activation mechanisms differing between high-dose and low-dose irradiation. High-dose irradiation activates macrophages directly, whereas low-dose irradiation acts indirectly through interaction with neighboring cells and the paracrine induction of cytokines. In this review, we discuss the augmentation of NO production in macrophages by ionizing radiation and its mechanism and significance. In radiotherapy, the control of NO levels both in whole-body and in the tumor is important to prevent irradiation-induced injury and for the cancer to regress.