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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1430080

Interleukin-10 contrasts inflammatory synaptopathy and central neurodegenerative damage in multiple sclerosis

Provisionally accepted
Luana Gilio Luana Gilio 1,2Diego Fresegna Diego Fresegna 3,4Mario Stampanoni Bassi Mario Stampanoni Bassi 5Alessandra Musella Alessandra Musella 3,6Francesca De Vito Francesca De Vito 5Sara Balletta Sara Balletta 5Krizia Sanna Krizia Sanna 4Silvia Caioli Silvia Caioli 5Luigi Pavone Luigi Pavone 5Giovanni Galifi Giovanni Galifi 4,5Ilaria Simonelli Ilaria Simonelli 7,8Livia Guadalupi Livia Guadalupi 3,4Valentina Vanni Valentina Vanni 3Fabio Buttari Fabio Buttari 4,5Ettore Dolcetti Ettore Dolcetti 4,5Antonio Bruno Antonio Bruno 4,9Federica Azzolini Federica Azzolini 9Angela Borrelli Angela Borrelli 5Roberta Fantozzi Roberta Fantozzi 5Annamaria Finardi Annamaria Finardi 10Roberto Furlan Roberto Furlan 10,11Diego Centonze Diego Centonze 1,4*Georgia Mandolesi Georgia Mandolesi 3,6
  • 1 Neuroscience, Unit of Neurology, IRCCS Neuromed, Pozzilli (IS), Italy
  • 2 Faculty of Psychology, Uninettuno Telematic International University, Rome, Sicily, Italy
  • 3 Synaptic Immunopathology Lab, IRCCS San Raffaele Roma, Italy, Rome, Sicily, Italy
  • 4 Department of Systems Medicine, Faculty of Medicine and Surgery, University of Rome Tor Vergata, Rome, Lazio, Italy
  • 5 Unit of Neurology, IRCCS Neuromed, Pozzilli (IS), Italy
  • 6 Department of Human Sciences and Quality of Life Promotion, University of Rome San Raffaele, Italy, Rome, Sicily, Italy
  • 7 Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Lazio, Italy
  • 8 Fatebenefratelli Hospital, Rome, Lazio, Italy
  • 9 Unit of Neurology, IRCCS Neuromed, Pozzilli (IS), Italy, Pozzilli (IS), Italy
  • 10 Clinical Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Lombardy, Italy
  • 11 Vita-Salute San Raffaele University, Milan, Lombardy, Italy

The final, formatted version of the article will be published soon.

    Proinflammatory cytokines are implicated in promoting neurodegeneration in multiple sclerosis (MS) by affecting excitatory and inhibitory transmission at central synapses. Conversely, the synaptic effects of anti-inflammatory molecules remain underexplored, despite their potential neuroprotective properties and their presence in the cerebrospinal fluid (CSF) of patients.In a study involving 184 newly diagnosed relapsing-remitting (RR)-MS patients, we investigated whether CSF levels of the anti-inflammatory interleukin (IL)-10 were linked to disease severity and neurodegeneration measures. Additionally, we examined IL-10 impact on synaptic transmission in striatal medium spiny neurons and its role in counteracting inflammatory synaptopathy induced by IL-1β in female C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE).Our findings revealed a significant positive correlation between IL-10 CSF levels and changes in EDSS (Expanded Disability Status Scale) scores one year after MS diagnosis. Moreover, IL-10 levels in the CSF were positively correlated with volumes of specific subcortical brain structures, such as the nucleus caudate.In both MS patients' CSF and EAE mice striatum, IL-10 and IL-1β expressions were upregulated, suggesting possible antagonistic effects of these cytokines. Notably, IL-10 exhibited the ability to decrease glutamate transmission, increase GABA transmission in the striatum, and reverse IL-1βinduced abnormal synaptic transmission in EAE.In conclusion, our data suggest that IL-10 exerts direct neuroprotective effects in MS patients by modulating both excitatory and inhibitory transmission and attenuating IL-1β-induced inflammatory synaptopathy. These findings underscore the potential therapeutic significance of IL-10 in mitigating neurodegeneration in MS.

    Keywords: IRCCS Neuromed, 86077 Pozzilli (IS), Italy Multiple Sclerosis, Interleukin-10, interleukin-1β, Experimental autoimmune encephalomyelitis (EAE), GABA transmission, glutamate transmission

    Received: 09 May 2024; Accepted: 22 Jul 2024.

    Copyright: © 2024 Gilio, Fresegna, Stampanoni Bassi, Musella, De Vito, Balletta, Sanna, Caioli, Pavone, Galifi, Simonelli, Guadalupi, Vanni, Buttari, Dolcetti, Bruno, Azzolini, Borrelli, Fantozzi, Finardi, Furlan, Centonze and Mandolesi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Diego Centonze, Neuroscience, Unit of Neurology, IRCCS Neuromed, Pozzilli (IS), 00133, Italy

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