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Site‐specific targeting of autoimmunity in mice induced by the localized production of IL‐6
Author(s) -
Campbell Iain Leslie,
Quintana Albert,
Müller Marcus,
Frausto Ricardo,
Getts Daniel,
King Nicholas J.,
Hofer Markus J.,
Hidalgo Juan
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.664.3
Subject(s) - cerebellum , spinal cord , immunology , experimental autoimmune encephalomyelitis , ataxia , autoimmunity , chemokine , genetically modified mouse , immune system , biology , medicine , endocrinology , transgene , neuroscience , biochemistry , gene
IL‐6 is required for the induction of experimental autoimmunity. The role of IL‐6 in EAE was examined in transgenic mice (GF‐IL6) with cerebellum specific production of IL‐6. MOG‐immunized (Mi‐) GF‐IL6 mice developed severe ataxia which was in contrast to Mi‐wild type (WT) mice that developed classical EAE with hind limb paralysis. Immune pathology and demyelination were markedly decreased in the spinal cord but significantly increased in the cerebellum of Mi‐GF‐IL6 mice. Tissue damage in the cerebellum at peak disease in the Mi‐GF‐IL6 mice was accompanied by increased total numbers of infiltrating leukocytes and increased proportions of both neutrophils and B‐cells. During peak disease, the expression of various cytokines was found at comparable levels in the cerebellum between Mi‐GF‐IL6 and Mi‐WT, whereas significantly higher levels were found in Mi‐WT spinal cord. In conclusion, site‐specific production of IL‐6 targets and modifies the autoreactive inflammatory response and creates a leukocyte “sink” that retards trafficking to normally dominant antigenic sites. The mechanisms underlying this response to IL‐6 likely include the induction of specific chemokines as well as increased activation and loss of integrity of the BBB in the cerebellum of the GF‐IL6 mice observed prior to the induction of EAE. Support:NSW Spinal Cord Injury and Other Neurological Conditions Project Grant.