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Acceleration of scrapie in mice by target-organ treatment with interferon inducers
Abstract:
Interferon inducers were used in the target-organ treatment of scrapie in mice. Intracerebral treatments began 24 hr prior to intracerebral inoculation of 10(4.8) LD50 of the Chandler strain of scrapie agent. The treatments included 30 and 0.3 microgram poly(I:C) given weekly 9 times, 45 microgram statolon given biweekly 7 times, or 1.5 HA units of Sendai virus given biweekly 6 times. All treatments except the lower dose of poly(I:C) accelerated death in scrapie-affected mice. Compared to saline-treated control groups, 30 microgram poly(I:C), given weekly, shortened the mean survival time 13.5 days. Groups treated with statolon or Sendai virus had their mean survival times shortened 18.5 and 21.7 days, respectively. Infected mice were also evaluated for signs of disease at approximately weekly intervals using a numerical scoring method. Acceleration was also apparent using this parameter of disease. When treatment occurred only once, Sendai virus was the only inducer to significantly shorten the survival of mice.
Insights
Interferon inducers like poly(I:C), statolon, and Sendai virus were tested for scrapie treatment in mice. Most inducers accelerated disease progression and shortened survival times.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Scrapie is a fatal neurodegenerative disease caused by prions.
- Interferon inducers modulate the immune system and have been explored for antiviral and anticancer properties.
Purpose of the Study:
- To investigate the effect of interferon inducers on scrapie progression in a mouse model.
- To determine if intracerebral administration of interferon inducers could alter the course of scrapie disease.
Main Methods:
- Mice were inoculated intracerebrally with the Chandler strain of scrapie agent.
- Interferon inducers, including poly(I:C), statolon, and Sendai virus, were administered intracerebrally before and after infection.
- Survival times and disease progression were monitored using clinical scoring.
Main Results:
- All treatments, except low-dose poly(I:C), accelerated mortality in scrapie-infected mice.
- Poly(I:C) (30 µg weekly) shortened mean survival by 13.5 days.
- Statolon and Sendai virus shortened mean survival by 18.5 and 21.7 days, respectively.
- Disease acceleration was confirmed by clinical scoring.
Conclusions:
- Intracerebral administration of interferon inducers can accelerate scrapie disease progression in mice.
- The findings suggest that modulating the immune response with interferon inducers may exacerbate prion diseases.
- Further research is needed to understand the mechanisms underlying this acceleration.
