title: IL-17 and glutamate excitotoxicity in the pathogenesis of multiple sclerosis.
abstract: Immunoinflammatory-mediated demyelination, the main pathological feature of multiple sclerosis (MS), is regularly accompanied by neurodegenerative processes, mostly in the form of axonal degeneration, which could be initiated by glutamate excitotoxicity. In the current study, the relationship between Th17-mediated inflammatory and excitotoxic events was investigated during an active phase of MS. Cerebrospinal fluid (CSF) of patients with MS and control subjects was collected, and IL-17A and glutamate levels were determined. IL-17A level was significantly higher in patients with MS; whereas no statistically significant changes in glutamate concentrations were found. There was a direct correlation between IL-17A and glutamate levels; IL-17A levels were also associated with the neutrophil expansion in CSF and blood-brain barrier disruption. However, IL-17A level and the number of neutrophils tended to fall with disease duration. The results suggest that Th17 cells might enhance and use glutamate excitotoxicity as an effector mechanism in the MS pathogenesis. Furthermore, Th17 immune response, as well as neutrophils, could be more important for MS onset rather than further disease development and progression, what could explain why some MS clinical trials, targeting Th17 cells in the later stage of the disease, failed to provide any clinical benefit.
authors.affiliation: Department of Immunology, Medical Faculty, University of Nis, Nis, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Kostic
authors.forename: T
authors.initials: T
authors.lastname: Dzopalic
authors.forename: S
authors.initials: S
authors.lastname: Zivanovic
authors.forename: N
authors.initials: N
authors.lastname: Zivkovic
authors.forename: A
authors.initials: A
authors.lastname: Cvetanovic
authors.forename: I
authors.initials: I
authors.lastname: Stojanovic
authors.forename: S
authors.initials: S
authors.lastname: Vojinovic
authors.forename: G
authors.initials: G
authors.lastname: Marjanovic
authors.forename: V
authors.initials: V
authors.lastname: Savic
authors.forename: M
authors.initials: M
authors.lastname: Colic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001812:Blood-Brain Barrier / Q000276:immunology; D005260:Female; D018698:Glutamic Acid / Q000134:cerebrospinal fluid* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D018698:Glutamic Acid