[Multiple sclerosis]

Abstract

Longitudinally extensive spinal cord lesions that extend over three vertebral segments on magnetic resonance imaging (MRI) are significantly more common in opticospinal multiple sclerosis (OSMS) than in conventional MS (CMS) in Japanese. In Japanese patients with MS, concentrations of serum vascular endothelial growth factor (VEGF) were significantly higher in MS patients in relapse than in controls or MS patients in remission, irrespective of clinical subtype. VEGF at relapse showed a significant positive correlation with the length of the spinal cord lesions on MRI. The IL-17/IL-8 system in cerebrospinal fluid (CSF) was markedly activated in OSMS, and both cytokines correlated with CSF/serum albumin ratio and the spinal cord lesion length on MRI. IL-17 is produced by autoreactive memory T cells and induces IL-8 production in a variety of cells. IL-8 acts as a chemokine for neutrophils as well as T cells. In autopsied spinal cords from OSMS patients, many neutrophils were seen to infiltrate the severely damaged spinal cord lesions; something that might be explained by intrathecal activation of IL-17/IL-8 axis in this condition. Our results, therefore, suggest that an increase in both serum VEGF and CSF IL-17 and IL-8 might contribute to the formation of longitudinally extensive spinal cord lesions through an increase of vascular permeability and the reinforcement of neutrophilic inflammation.