Effects of low-dose irradiation on mice with Escherichia coli-induced sepsis

Toxicol Appl Pharmacol. 2017 Oct 15:333:17-25. doi: 10.1016/j.taap.2017.08.008. Epub 2017 Aug 14.

Abstract

Although favorable immune responses to low-dose irradiation (LDI) have been observed in normal mice, i.e., a hormesis effect, little is known about the effects of LDI in infectious diseases. In this study, we examined the effects of LDI on mice with sepsis, a severe and often lethal hyperinflammatory response to bacteria. Female C57BL/6 mice were whole-body irradiated with 10cGy 48h before Escherichia coli infection, and survival, bacterial clearance, cytokines, and antioxidants were quantified. LDI pretreatment significantly increased survival from 46.7% in control mice to 75% in mice with sepsis. The bacterial burden was significantly lower in the blood, spleen, and kidney of LDI-treated mice than in those of control septic mice. The levels of pro-inflammatory cytokines, e.g., IL-1β and IL-6, as well as anti-inflammatory IL-10 were markedly reduced in pre-LDI septic mice. Nitric oxide production by peritoneal macrophages was also reduced in pre-LDI septic mice. Immune cells in the spleen increased and Nrf2 and HO-1 were induced in pre-LDI septic mice. LDI stimulates the immune response and minimizes lethality in septic mice via enhanced bacterial clearance and reduced initial proinflammatory responses.

Keywords: Antioxidant; Immune response; Inflammation; Low-dose irradiation; Sepsis.

MeSH terms

  • Animals
  • Colony Count, Microbial
  • Cytokines / blood
  • Escherichia coli / isolation & purification
  • Escherichia coli Infections / blood
  • Escherichia coli Infections / immunology
  • Escherichia coli Infections / microbiology
  • Escherichia coli Infections / radiotherapy*
  • Female
  • Kidney / microbiology
  • Kidney / radiation effects
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / metabolism
  • RAW 264.7 Cells
  • Sepsis / blood
  • Sepsis / immunology
  • Sepsis / microbiology
  • Sepsis / radiotherapy*
  • Spleen / microbiology
  • Spleen / radiation effects
  • Whole-Body Irradiation*

Substances

  • Cytokines
  • Nitric Oxide