Reduced secretion of the inflammatory cytokine IL-1β by stimulated peritoneal macrophages of radiosensitive Balb/c mice after exposure to 0.5 or 0.7Gy of ionizing radiation

Abstract

Since the beginning of the 20th century, low dose radiotherapy (LD-RT) has been practiced and established as therapy of inflammatory diseases. Several clinical studies already have proven the anti-inflammatory effect of low doses of ionizing irradiation (LDR). However, further research is inevitable to reveal the underlying immune-biological mechanisms. Focus has been set on the modulation of activated macrophages by LDR, since they participate in both, initiation and resolution of inflammation. Here we examined with an ex vivo peritoneal mouse macrophage model how LDR modulates the secretion of the inflammatory cytokines IL-1β and TNF-α by activated macrophages and whether the basal radiosensitivity of the immune cells has influence on it. Peritoneal macrophages of Balb/c mice responded to exposure of 0.5 or 0.7 Gy of ionizing irradiation (X-ray) with significant decreased release of IL-1β and slightly, but not significantly, reduced release of TNF-α. Macrophages of the less radiosensitive C57BL/6 mice did not show this anti-inflammatory reaction. This was observed in both wild type and human TNF-α transgenic animals with C57BL/6 background. We conclude that only the inflammatory phenotype of more radiosensitive macrophages is reduced by LDR and that ex vivo and in vivo models with primary cells should be applied to examine how the immune system is modulated by LDR.

Keywords::

• low dose ionizing irradiation
• anti-inflammation
• macrophages
• radiosensitivity
• Balb/c mice
• C57BL/6 mice
• hTNF-tg mice

Declaration of interest: This work was supported by the European Commissions (DoReMi, European Network of Excellence, contract number 249689), the German Federal Ministry of Education and Research (BMBF; GREWIS, 02NUK017G) and by the Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nuremberg (project A41). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.