Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis

There are two distinct subtypes of multiple sclerosis in Asians, opticospinal (OS-multiple sclerosis) and conventional (C-multiple sclerosis). In OS-multiple sclerosis, selective and severe involvement of the optic nerves and spinal cord is characteristic, though its mechanisms are unknown. The pres...

Full description

Saved in:
Bibliographic Details
Published in:Brain (London, England : 1878) England : 1878), 2005-05, Vol.128 (5), p.988-1002
Main Authors: Ishizu, Takaaki, Osoegawa, Manabu, Mei, Feng-Jun, Kikuchi, Hitoshi, Tanaka, Masahito, Takakura, Yuka, Minohara, Motozumi, Murai, Hiroyuki, Mihara, Futoshi, Taniwaki, Takayuki, Kira, Jun-ichi
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biological and medical sciences
C-multiple sclerosis = conventional form of multiple sclerosis
CD4-Positive T-Lymphocytes - immunology
cerebrospinal fluid
chemokine
Chemokines - cerebrospinal fluid
cytokine
Cytokines - blood
Cytokines - cerebrospinal fluid
EAE = experimental allergic encephalomyelitis
EDSS = Expanded Disability Status Scale of Kurtzke
Female
G-CSF = granulocyte colony-stimulating factor
Humans
IFN = interferon
IL = interleukin
Immunomodulators
Interleukin-17 - cerebrospinal fluid
Interleukin-8 - cerebrospinal fluid
LP = lumbar puncture
Magnetic Resonance Imaging
Male
MCP-1 = monocyte chemoattractant protein-1
Medical sciences
Middle Aged
MIP-1β = macrophage inflammatory protein-1β
multiple sclerosis
Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis
Neurology
Neuromyelitis Optica - cerebrospinal fluid
Neuromyelitis Optica - immunology
Neuromyelitis Optica - pathology
neutrophil
Neutrophil Infiltration
NMO = neuromyelitis optica
OS-multiple sclerosis = opticospinal form of multiple sclerosis
PBL = peripheral blood lymphocyte
Pharmacology. Drug treatments
SCD = spinocerebellar degeneration
Spinal Cord - pathology
TNF = tumour necrosis factor
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:There are two distinct subtypes of multiple sclerosis in Asians, opticospinal (OS-multiple sclerosis) and conventional (C-multiple sclerosis). In OS-multiple sclerosis, selective and severe involvement of the optic nerves and spinal cord is characteristic, though its mechanisms are unknown. The present study aimed to find out possible differences in the cytokine/chemokine profiles in CSF between OS-multiple sclerosis and C-multiple sclerosis and to delineate the relationships between these profiles and neuroimaging and pathological features. Sixteen cytokines/chemokines, namely interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β), were measured simultaneously in CSF supernatants from 40 patients with relapsing–remitting multiple sclerosis (20 OS-multiple sclerosis and 20 C-multiple sclerosis) at relapse and 19 control patients with spinocerebellar degeneration (SCD), together with intracellular production of IFN-γ and IL-4 in CSF CD4+ T cells. In CSF supernatants relative to controls, IL-17, MIP-1β, IL-1β and IL-13 were only significantly increased in OS-multiple sclerosis patients, while TNF-α was only significantly increased in C-multiple sclerosis patients, using a cut-off level of 1 pg/ml. IL-8 was significantly elevated in both OS-multiple sclerosis and C-multiple sclerosis patients. MCP-1 was significantly decreased in both OS-multiple sclerosis and C-multiple sclerosis patients, while IL-7 was only significantly decreased in C-multiple sclerosis patients. IL-17, IL-8 and IL-5 were significantly higher in OS-multiple sclerosis patients than in C-multiple sclerosis patients. The increases in IL-17 and IL-8 in OS-multiple sclerosis were still significant even after exclusion of the patients undergoing various immunomodulatory therapies. Assays of intracellular cytokine production revealed that both the IFN-γ+IL-4− T-cell percentage and intracellular IFN-γ/IL-4 ratio in CSF cells were significantly greater in C-multiple sclerosis patients than in controls. Contrarily, OS-multiple sclerosis patients showed not only a significantly greater percentage of IFN-γ+IL-4− T cells than controls but also a significantly higher percentage of IFN-γ−IL-4+ T cells than C-multiple sclerosis patients. Among the cytokines elevated in multiple scle
ISSN:0006-8950
1460-2156
DOI:10.1093/brain/awh453