Intracerebral administration of interleukin-12 (IL-12) and IL-18 modifies the course of mouse scrapie

Abstract

Background: Prion diseases are characterised by a neurodegenerative pattern in which the function of immune system remains still elusive. In the present study, we evaluate if an exogenous treatment with Interleukin-12 (IL-12) and IL-18, able to activate microglia, is able to affect scrapie pathogenesis.

Results: Cytokines injected intracranially, induced a strong inflammatory response characterised by TNF-alpha production and microglia activation. Two groups of mice were injected intracerebrally with high dose of ME7 strain of scrapie containing IL-12 and IL-18 or sterile saline. Cytokines-treated mice showed a more pronounced accumulation of PrPSc in brain tissues at 90 days post-inoculation and a shorter mean survival times than untreated mice.

Conclusion: We can conclude that intracerebral administration of IL-12 and IL-18 can modulate scrapie pathogenesis possibly through a microglia-mediated pattern.

Figure 1

IFN-γ production. IFN-γ production, detected in brain homogenates, from untreated mice or mice intracerebrally inoculated with saline or IL-12 and IL-18, sacrificed at different time after treatment. * values statistically different from those obtained in mice treated with saline at the same time.

Figure 2

TNF-α production. TNF-α production detected in brain homogenates, from untreated mice or mice intracerebrally inoculated with saline or IL-12 and IL-18, sacrificed at different time after treatment. *values statistically different from those obtained in mice treated with saline at the same time

Figure 3

Survival of scrapie infected mice. Survival times after intracerebrally injection of scrapie ME7-derived brain homogenate (10% w/v in sterile saline) of mice treated with IL-12 and IL-18 (circles) or with saline (squares).

Figure 4

PrPsc evaluation. Western-blot patterns (A, C) and semiquantitative analysis (B, D) of brain homogenates of mice sacrificed at 90 days after infection (A, B) or terminally sick (C, D).