NR ARKN
AU Thackray,A.M.; McKenzie,A.N.; Klein,M.A.; Lauder,A.; Bujdoso,R.
TI Accelerated prion disease in the absence of interleukin-10
QU Journal of Virology 2004 Dec; 78(24): 13697-707
PT journal article
AB The identity of pro- and anti-inflammatory cytokines in the neuropathogenesis of prion diseases remains undefined. Here we have investigated the role of anti-inflammatory cytokines on the progression of prion disease through the use of mice that lack interleukin-4 (IL-4), IL-10, IL-13, or both IL-4 and IL-13. Collectively our data show that among these anti-inflammatory cytokines, IL-10 plays a prominent role in the regulation of prion disease. Mice deficient in IL-10 are highly susceptible to the development of prion disease and show a markedly shortened incubation time. In addition, we have correlated cytokine gene expression in prion-inoculated IL-10(-/-) mice to wild-type-inoculated animals. Our experiments show that in the absence of IL-10 there is an early expression of tumor necrosis factor alpha (TNF-alpha). In wild-type prion-inoculated mice, the expression of TNF-alpha mRNA occurs at a later time point that correlates with the extended incubation time for terminal disease development in these animals compared to those that lack IL-10. Elevated levels of IL-13 mRNA are found at early time points in the central nervous system of prion-inoculated IL-10(-/-) mice. At terminal disease, the brains of wild-type mice inoculated with RML or ME7 are characterized by elevated levels of mRNA for the proinflammatory cytokines TNF-alpha and IL-1ß, together with the anti-inflammatory cytokines IL-10, IL-13, and transforming growth factor beta. Our data are consistent with a role for proinflammatory cytokines in the initiation of pathology during prion disease and an attempt by anti-inflammatory cytokines to regulate the ensuing, invariably fatal pathology.
IN Wenn Hausmäuse (RML- oder ME7-) kein Interleukin 10 produzieren können, dann ist ihre Empfänglichkeit für TSE-Infektionen erhöht, ihre Inkubationszeiten sind verkürzt und sie exprimieren früher als Wildtyp-Hausmäuse nach der Inokulation den Tumornekrosefaktor alpha.
MH Animals; Brain/immunology/metabolism/pathology; Female; Interleukin-10/genetics/*metabolism; Interleukins/genetics/metabolism; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; PrPsc Proteins/pathogenicity; Prion Diseases/*immunology/*physiopathology; Research Support, Non-U.S. Gov't; Spleen/immunology/metabolism/pathology; Tumor Necrosis Factor-alpha/genetics/metabolism
AD Centre for Veterinary Science, Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 OES, United Kingdom.
SP englisch
PO USA