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

Abstract

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...

Clinical characteristics of neuro-Behcet’s disease in Japan: a multicenter retrospective analysis

“…Consistently, in the present study, CSF IL-6 was elevated in acute NBD as well as in CP NBD, but not in non-NBD. Previous studies demonstrated that CSF IL-6 was not elevated in patients with multiple sclerosis [22, 23]. Therefore, the determination of CSF IL-6 might be useful for the differential diagnosis of NBD and multiple sclerosis.…”

Development of an anti‐IL‐17A auto‐vaccine that prevents experimental auto‐immune encephalomyelitis

“…It offers great hope for potential treatment of diseases where IL-17 is recognized as the key inducer of inflammation, as is now Highlights 2871 well documented in arthritis [29], asthma [30], inflammatory bowel disease [31,32] and intra-abdominal abscesses [33]. In multiple sclerosis, little is known about the actual importance of IL-17, although increased numbers of IL-17 mRNA-expressing cells were found to correlate with disease exacerbation [34]. Another question that remains to be solved, is whether anti-IL-17 vaccination can be effective curatively.…”

Glial and Axonal Pathology in Multiple Sclerosis

“…IL-17-producing T-helper cells play an important role in the induction of neuroimmune diseases, like MS and its animal model called experimental autoimmune encephalomyelitis (EAE) [Iwakura & Ishigame, 2006.]. This observation is based on the detection of IL-17 levels in both the plaques and cerebrospinal fluid of MS patients [Ishizu et al, 2005].…”