PMID- 15743872
OWN - NLM
STAT- MEDLINE
DCOM- 20050610
LR  - 20061115
IS  - 1460-2156 (Electronic)
IS  - 0006-8950 (Linking)
VI  - 128
IP  - Pt 5
DP  - 2005 May
TI  - Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis.
PG  - 988-1002
AB  - 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)-1beta, IL-2, IL-4, IL-5, IL-6, 
      IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, interferon (IFN)-gamma, tumour 
      necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), 
      monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory 
      protein-1beta (MIP-1beta), 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-gamma and IL-4 in CSF CD4+ T cells. In CSF supernatants relative to controls, 
      IL-17, MIP-1beta, IL-1beta and IL-13 were only significantly increased in 
      OS-multiple sclerosis patients, while TNF-alpha 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-gamma+IL-4- T-cell percentage and intracellular IFN-gamma/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-gamma+IL-4- T cells than controls but 
      also a significantly higher percentage of IFN-gamma-IL-4+ T cells than C-multiple 
      sclerosis patients. Among the cytokines elevated in multiple sclerosis, only IL-8 
      showed a significant positive correlation with the Expanded Disability Status 
      Scale of Kurtzke score. Both the length of the spinal cord lesions on MRI and the 
      CSF/serum albumin ratio had a significant positive correlation with IL-8 and 
      IL-17 in multiple sclerosis, in which the spinal cord lesions were significantly 
      longer in OS-multiple sclerosis than in C-multiple sclerosis. Three of six spinal 
      cord specimens from autopsied OS-multiple sclerosis cases demonstrated numerous 
      myeloperoxidase-positive neutrophils infiltrating necrotic lesions. These 
      findings strongly suggest that in OS-multiple sclerosis, in addition to the Th1 
      cell upregulation seen in C-multiple sclerosis, intrathecal activation of the 
      IL-17/IL-8 axis inducing heavy neutrophil infiltration contributes to extensive 
      spinal cord lesion formation.
FAU - Ishizu, Takaaki
AU  - Ishizu T
AD  - Department of Neurology, Neurological Institute, Department of Radiology, 
      Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
FAU - Osoegawa, Manabu
AU  - Osoegawa M
FAU - Mei, Feng-Jun
AU  - Mei FJ
FAU - Kikuchi, Hitoshi
AU  - Kikuchi H
FAU - Tanaka, Masahito
AU  - Tanaka M
FAU - Takakura, Yuka
AU  - Takakura Y
FAU - Minohara, Motozumi
AU  - Minohara M
FAU - Murai, Hiroyuki
AU  - Murai H
FAU - Mihara, Futoshi
AU  - Mihara F
FAU - Taniwaki, Takayuki
AU  - Taniwaki T
FAU - Kira, Jun-ichi
AU  - Kira J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050302
PL  - England
TA  - Brain
JT  - Brain : a journal of neurology
JID - 0372537
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-8)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Chemokines/cerebrospinal fluid
MH  - Cytokines/blood/cerebrospinal fluid
MH  - Female
MH  - Humans
MH  - Interleukin-17/*cerebrospinal fluid
MH  - Interleukin-8/*cerebrospinal fluid
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Neuromyelitis Optica/*cerebrospinal fluid/immunology/pathology
MH  - Neutrophil Infiltration
MH  - Spinal Cord/pathology
EDAT- 2005/03/04 09:00
MHDA- 2005/06/11 09:00
CRDT- 2005/03/04 09:00
PHST- 2005/03/04 09:00 [pubmed]
PHST- 2005/06/11 09:00 [medline]
PHST- 2005/03/04 09:00 [entrez]
AID - awh453 [pii]
AID - 10.1093/brain/awh453 [doi]
PST - ppublish
SO  - Brain. 2005 May;128(Pt 5):988-1002. doi: 10.1093/brain/awh453. Epub 2005 Mar 2.