title: Cytokine production profiles in chronic relapsing-remitting experimental autoimmune encephalomyelitis: IFN-γ and TNF-α are important participants in the first attack but not in the relapse.
abstract: Multiple sclerosis (MS) is a chronic demyelinating disease often displaying a relapsing-remitting course of neurological manifestations that is mimicked by experimental autoimmune encephalomyelitis (EAE) in animal models of MS. In particular, NOD mice immunized with myelin oligodendrocyte glycoprotein peptide 35-55 develop chronic relapsing-remitting EAE (CREAE). To elucidate the mechanisms that cause MS relapse, we investigated the histopathology and cytokine production of spleen cells and mRNA expression levels in the central nervous system (CNS) of CREAE mice. During the first attack, inflammatory cell infiltration around small vessels and in the subarachnoid space was observed in the spinal cord. Spleen cell production and mRNA expression in the CNS of several cytokines, including IFN-γ, TNF-α, IL-6, IL-17, and CC chemokine ligand 2 (CCL2), were higher in CREAE mice than in controls. Afterwards, parenchymal infiltration and demyelination were observed histologically in the spinal cord and corresponded with the more severe clinical symptoms of the first and second relapses. IL-17 and CCL2, but not IFN-γ, TNF-α, or IL-6, were also produced by spleen cells during recurrences. Our results suggested that the immune mechanisms in relapses were different from those in the first attack for CREAE. Further investigation of CREAE mechanisms may provide important insights into successful therapies for human relapsing-remitting MS.
authors.affiliation: Department of Pediatrics, School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hidaka
authors.affiliation: Department of Pediatrics, School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. Electronic address: inabay@shinshu-u.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Inaba
authors.affiliation: Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Department of Pathology and Laboratory Medicine, Kariya Toyota General Hospital, 5-15 Sumiyoshi, Kariya, Aichi 448-8505, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Itoh
authors.affiliation: Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kaneyama
authors.affiliation: Department of Pediatrics, School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Nakazawa
authors.affiliation: Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Chang-Sung
authors.initials: CS
authors.lastname: Koh
authors.affiliation: Child and Women's Health Sciences, Graduate School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Ichikawa
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D051379:Mice; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000473:pathology; D013997:Time Factors
chemical_list: D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger; C445081:myelin oligodendrocyte glycoprotein (35-55); D005620:Freund's Adjuvant
keywords: CC chemokine ligand 2 (CCL2); Chronic relapsing–remitting experimental autoimmune encephalomyelitis (CREAE); Interferon-γ (IFN-γ); Interleukin-6 (IL-6); Multiple sclerosis; Tumor necrosis factor-α (TNF-α)