title: Induction of atypical EAE mediated by transgenic production of IL-6 in astrocytes in the absence of systemic IL-6.
abstract: Interleukin (IL)-6 is crucial for the induction of many murine models of autoimmunity including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. While IL-6-deficient mice (IL-6 KO) are resistant to EAE, we showed previously that in transgenic mice with astrocyte-targeted production of IL-6-restricted to the cerebellum (GFAP-IL6), EAE induced with MOG(35-55) was redirected away from the spinal cord to the cerebellum. To further establish the importance of IL-6 produced in the central nervous system, we have generated mice producing IL-6 essentially only in the brain by crossing the GFAP-IL6 mice with IL-6 KO mice. Interestingly, GFAP-IL6-IL-6 KO mice showed a milder but almost identical phenotype as the GFAP-IL6 mice, which correlated with a lower load of inflammatory cells and decreased microglial reactivity. These results indicate that not only is cerebellar IL-6 production and eventual leakage into the peripheral compartment the dominating factor controlling this type of EAE but that it can also facilitate induction of autoimmunity in the absence of normal systemic IL-6 production.
authors: Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Mercedes
authors: M
authors: Giralt
authors: Raquel
authors: R
authors: Ramos
authors: Albert
authors: A
authors: Quintana
authors: Beatriz
authors: B
authors: Ferrer
authors: Maria
authors: M
authors: Erta
authors: Marco
authors: M
authors: Castro-Freire
authors: Gemma
authors: G
authors: Comes
authors: Elisenda
authors: E
authors: Sanz
authors: Mercedes
authors: M
authors: Unzeta
authors: Paula
authors: P
authors: Pifarré
authors: Agustina
authors: A
authors: García
authors: Iain L
authors: IL
authors: Campbell
authors: Juan
authors: J
authors: Hidalgo
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic
chemical_list: D015850:Interleukin-6; C577686:interleukin-6, mouse