<scp>IL</scp>‐17 and Glutamate Excitotoxicity in the Pathogenesis of Multiple Sclerosis

<jats:title>Abstract</jats:title><jats:p>Immunoinflammatory‐mediated demyelination, the main pathological feature of multiple sclerosis (<jats:styled-content style="fixed-case">MS</jats:styled-content>), 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 <jats:styled-content style="fixed-case">MS</jats:styled-content>. Cerebrospinal fluid (<jats:styled-content style="fixed-case">CSF</jats:styled-content>) of patients with <jats:styled-content style="fixed-case">MS</jats:styled-content> and control subjects was collected, and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17A and glutamate levels were determined. <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17A level was significantly higher in patients with <jats:styled-content style="fixed-case">MS</jats:styled-content>; whereas no statistically significant changes in glutamate concentrations were found. There was a direct correlation between <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17A and glutamate levels; <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17A levels were also associated with the neutrophil expansion in <jats:styled-content style="fixed-case">CSF</jats:styled-content> and blood–brain barrier disruption. However, <jats:styled-content style="fixed-case">IL</jats:styled-content>‐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 <jats:styled-content style="fixed-case">MS</jats:styled-content> pathogenesis. Furthermore, Th17 immune response, as well as neutrophils, could be more important for <jats:styled-content style="fixed-case">MS</jats:styled-content> onset rather than further disease development and progression, what could explain why some <jats:styled-content style="fixed-case">MS</jats:styled-content> clinical trials, targeting Th17 cells in the later stage of the disease, failed to provide any clinical benefit.</jats:p>