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


CONCLUSIONS
We can conclude that intracerebral administration of IL-12 and IL-18 can modulate scrapie pathogenesis possibly through a microglia-mediated pattern.
Pasquali
Paolo
P
Department of Food Safety and Animal Health, Istituto Superiore di Sanità, viale Regina Elena 299, 00161, Rome, Italy. paolo.pasquali@iss.it
Nonno
Romolo
R
Mandara
Maria Teresa
MT
Di Bari
Michele Angelo
MA
Ricci
Giovanni
G
Petrucci
Paola
P
Capuccini
Silvia
S
Cartoni
Claudia
C
Macrì
Agostino
A
Agrimi
Umberto
U
D000818:Animals; D004359:Drug Therapy, Combination; D005260:Female; D007276:Injections, Intraventricular; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000627:therapeutic use*; D020382:Interleukin-18 / Q000008:administration & dosage* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D012608:Scrapie / Q000188:drug therapy*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma