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Delayed treatment of MS is associated with high CSF levels of IL-6 and IL-8 and worse future disease course

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Abstract

Background

Clinical deterioration of relapsing–remitting MS (RR-MS) patients reflects not only the number and severity of overt inflammatory and demyelinating episodes, but also subtle central damage caused by persistent exposure to inflammatory molecules.

Objective

To explore the correlation between levels of CSF inflammatory molecules at the time of diagnosis and both demographic and clinical characteristics of a large sample of RR-MS patients, as well as the predictive value of cytokine levels on their prospective disease course.

Methods

In 205 patients diagnosed with RR-MS, we measured at the time of diagnosis the CSF levels of inflammatory molecules. Clinical and MRI evaluation was collected at the time of CSF withdrawal and during a median follow-up of 3 years.

Results

The time interval between the first anamnestic episode of focal neurological dysfunction and RR-MS diagnosis was the main factor associated with high CSF levels of IL-6 and IL-8. Furthermore, elevated CSF levels of these cytokines correlated with enhanced risk of clinical and radiological disease reactivation, switch to second-line treatments, and with disability progression in the follow-up.

Conclusions

Delayed diagnosis and treatment initiation are associated with higher CSF levels of IL-6 and IL-8 in RR-MS, leading to worsening disease course and poor response to treatments.

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Acknowledgements

The present study was supported by the Italian Ministry of Health (Ricerca Corrente), and by the 5 × 1000 grant to IRCCS Neuromed.

Author information

Authors and Affiliations

  1. Unit of Neurology and Neurorehabilitation, IRCCS Neuromed, Via Atinense 18, 86077, Pozzilli, IS, Italy

    Mario Stampanoni Bassi, Ennio Iezzi, Luana Gilio, Girolama A. Marfia, Diego Centonze & Fabio Buttari

  2. Multiple Sclerosis Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy

    Mario Stampanoni Bassi, Doriana Landi, Fabrizia Monteleone, Luana Gilio, Girolama A. Marfia & Diego Centonze

  3. Service of Medical Statistics and Information Technology, Fatebenefratelli Foundation for Health Research and Education, Rome, Italy

    Ilaria Simonelli

  4. Laboratory of Neuroimmunology and Synaptic Plasticity, IRCCS San Raffaele Pisana, Via di Val Cannuta 247, 00163, Rome, Italy

    Alessandra Musella, Georgia Mandolesi & Francesca De Vito

  5. Neuroimmunology Unit, Division of Neuroscience, Institute of Experimental Neurology (INSpe), San Raffaele Scientific Institute, Milan, Italy

    Roberto Furlan & Annamaria Finardi

Authors
  1. Mario Stampanoni Bassi
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  2. Ennio Iezzi
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  7. Alessandra Musella
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  9. Francesca De Vito
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  12. Girolama A. Marfia
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Contributions

MSB: conception and design of the study, drafting a significant portion of the manuscript or figures. EI: conception and design of the study, drafting a significant portion of the manuscript or figures. DL: acquisition and analysis of data. FM: acquisition and analysis of data. LG: acquisition and analysis of data. IS: statistical analysis of data. AM: acquisition and analysis of data. GM: acquisition and analysis of data. FV: acquisition and analysis of data. RF: analysis of data. AF: analysis of data. GAM: acquisition and analysis of data. DC: conception and design of the study, drafting a significant portion of the manuscript or figures. FB: conception and design of the study, drafting a significant portion of the manuscript or figures.

Corresponding author

Correspondence to Diego Centonze.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Stampanoni Bassi, M., Iezzi, E., Landi, D. et al. Delayed treatment of MS is associated with high CSF levels of IL-6 and IL-8 and worse future disease course. J Neurol 265, 2540–2547 (2018). https://doi.org/10.1007/s00415-018-8994-5

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  • DOI: https://doi.org/10.1007/s00415-018-8994-5

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