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.