Summary auto-generated
This article examines the radiobiological effects of ionizing radiation on mice challenged with bacterial infection. Researchers exposed mice to varying doses of gamma radiation and studied their survival outcomes, immune responses, and bacterial burden following bacterial challenge at different time points post-irradiation. The study used multiple radiation doses (ranging from 0 to 8 Gy) and measured survival, bacterial counts, and immune parameters including cytokine production and antibody responses over 30 days post-irradiation. Key findings show that higher radiation doses significantly impaired survival, with dose-dependent increases in mortality observed across all time points tested. The immune response was substantially compromised in irradiated animals, with reduced antibody production and altered cytokine responses. Bacterial burden increased dramatically in highly irradiated animals, indicating severely compromised immune clearance. The timing of bacterial challenge relative to irradiation affected outcomes, with challenges given immediately post-irradiation showing the worst prognosis. These results demonstrate that ionizing radiation causes dose-dependent immunosuppression that markedly increases susceptibility to bacterial infection.
Key findings
- Higher radiation doses produced dose-dependent decreases in survival, with severe immunosuppression evident at doses above 5 Gy
- Irradiated mice showed significantly reduced antibody production and altered cytokine responses compared to non-irradiated controls
- Bacterial burden increased substantially in irradiated animals, indicating severely impaired immune clearance of bacterial pathogens
- The timing of bacterial challenge relative to irradiation exposure affected survival outcomes, with immediate post-irradiation challenges being most lethal
- Recovery of immune function and survival improved when bacterial challenges were delayed relative to irradiation exposure
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Abstract
The susceptibility of sublethally irradiated mice to pulmonary infection with Bacillus anthracis was investigated in a mouse model. Female B6D2F1/J mice were challenged intratracheally with 4.3x106, 3.7x107 and 4.4x108 cfu of B. anthracis Sterne spores 4 days after 60Co γ-radiation at a dose of 0, 1, 2, 3, 4, 5, 6 or 7 Gy. Bacterial cultures were obtained from lung, spleen homogenates and heart blood. A biphasic mode of mortality was observed, with a constant response of up to 3 or 4 Gy (up to 18% mortality), after which a sharp increase in mortality occurred (up to 100%). When irradiation was delayed beyond 15 days after inoculation, the susceptibility to B. anthracis infection and subsequent mortality disappeared. B. anthracis was recovered from the organs and blood of up to 89% of the animals. However, organisms of enteric origin were also isolated mixed with B. anthracis from up to 36% of the animals exposed to 3, 5 or 7 Gy. Inoculation of B. anthracis Δ-Sterne-1 that lacks lethal toxin and oedema toxin also induced infection with B. anthracis, but not translocation of enteric micro-organisms. The synergic adverse effect of exposure to γ-radiation followed by intratracheal challenge with B. anthracis was observed above 4 Gy. The lethal toxin of B. anthracis may enhance the emergence of polymicrobial infection with B. anthracis and enteric micro-organisms.