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

被引:7
作者
Pasquali P. [1 ]
Nonno R. [1 ]
Mandara M.T. [2 ]
Di Bari M.A. [1 ]
Ricci G. [2 ]
Petrucci P. [1 ]
Capuccini S. [2 ]
Cartoni C. [1 ]
Macrì A. [1 ]
Agrimi U. [1 ]
机构
[1] Department of Food Safety and Animal Health, Istituto Superiore di Sanità, 00161, Rome
[2] Department of Biopathological Veterinary Science, Veterinary Medicine School, Università degli Studi di Perugia, Perugia
关键词
Prion Protein; Prion Disease; Brain Homogenate; Scrapie; Untreated Mouse;
D O I
10.1186/1746-6148-2-37
中图分类号
学科分类号
摘要
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-α 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. © 2006 Pasquali et al; licensee BioMed Central Ltd.
引用
收藏
相关论文
共 52 条
[1]  
Prusiner S.B., DeArmond S.J., Prion diseases and neurodegeneration, Annu Rev Neurosci, 17, pp. 311-339, (1994)
[2]  
Silveira J.R., Raymond G.J., Hughson A.G., Race R.E., Sim V.L., Hayes S.F., Caughey B., The most infectious prion protein particles, Nature, 437, pp. 257-261, (2005)
[3]  
Cunningham C., Wilcockson D.C., Boche D., Perry V.H., Comparison of inflammatory and acute-phase responses in the brain and peripheral organs of the ME7 model of prion disease, J Virol, 79, pp. 5174-5184, (2005)
[4]  
Porter D.D., Porter H.G., Cox N.A., Failure to demonstrate a humoral immune response to scrapie infection in mice, J Immunol, 111, pp. 1407-1410, (1973)
[5]  
Williams A.E., Lawson L.J., Perry V.H., Fraser H., Characterisation of the microglial response in murine scrapie, Neuropathol Appl Neurobiol, 20, pp. 47-55, (1994)
[6]  
Mabbott N.A., Bruce M.E., The immunobiology of TSE diseases, J Gen Virol, 82, pp. 2307-2318, (2001)
[7]  
Mabbott N.A., Mackay F., Minns F., Bruce M.E., Temporary inactivation of follicular dendritic cells delays neuroinvasion of scrapie, Nat Med, 6, pp. 719-720, (2000)
[8]  
Riemer C., Queck I., Simon D., Kurth R., Baier M., Identification of Upregulated Genes in Scrapie-Infected Brain Tissue, J Virol, 74, pp. 10245-11024, (2000)
[9]  
Xiang W., Windl O., Wunsch G., Dugas M., Kohlmann A., Dierkes N., Westner I.M., Kretzschmar H.A., Identification of differentially expressed genes in scrapie-infected mouse brains by using global gene expression technology, J Virol, 78, pp. 11051-11060, (2004)
[10]  
Outram G.W., Dickinson A.G., Fraser H., Reduced susceptibility to scrapie in mice after steroid administration, Nature, 249, pp. 855-856, (1974)