Contribution of Inflammatory Cytokine Release to Activation of Resident Peritoneal Macrophages after in vivo Low-dose γ-irradiation

The activation mechanism of resident peritoneal macrophages by in vivo gamma-irradiation was investigated. The function of macrophages as accessory cells in concanavalin A-induced proliferation of spleno-lymphocytes (accessory function) was enhanced 4 h after a low-dose irradiation (4 cGy) in vivo, but not in vitro, indicating that low-dose irradiation acts indirectly on the activation of macrophages. Because we expected that macrophages were activated by the recognition of substances damaged by in vivo irradiation, we co-cultured macrophages with oxidized erythrocyte-ghosts. No change was found in their accessory function. The production of inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma), in the supernatant of cocultures of spleno-lymphocytes and macrophages was determined by an ELISA. Production of both increased in the presence of in vivo irradiated macrophages. Furthermore, IL-1 beta production from in vivo-irradiated macrophages treated with recombinant IFN-gamma also was enhanced. The mRNA expression of the cytokines released from macrophages and lymphocytes was determined by RT-PCR. Increases in IL-1 beta mRNA expression were found in both in vivo- and in vitro-irradiated macrophages. In vivo irradiation also enhanced the expression of IFN-gamma mRNA in lymphocytes, whereas there was no change after in vitro irradiation. On the basis of these observations, we propose that the activation of macrophages is caused by interaction with neighboring cells, such as lymphocytes, and by paracrine induction of certain cytokines which is initiated by the small amount of IL-1 beta released by irradiated macrophages.