Journal of Neurology

, Volume 265, Issue 11, pp 2540–2547 | Cite as

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

  • Mario Stampanoni Bassi
  • Ennio Iezzi
  • Doriana Landi
  • Fabrizia Monteleone
  • Luana Gilio
  • Ilaria Simonelli
  • Alessandra Musella
  • Georgia Mandolesi
  • Francesca De Vito
  • Roberto Furlan
  • Annamaria Finardi
  • Girolama A. Marfia
  • Diego CentonzeEmail author
  • Fabio Buttari
Original Communication



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.


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.


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.


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.


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.


RR-MS CSF cytokines IL-6 IL-8 Neuroinflammation Disease activity 



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

Author 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.

Compliance with ethical standards

Conflicts of interest

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


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Unit of Neurology and NeurorehabilitationIRCCS NeuromedPozzilliItaly
  2. 2.Multiple Sclerosis Research Unit, Department of Systems MedicineTor Vergata UniversityRomeItaly
  3. 3.Service of Medical Statistics and Information TechnologyFatebenefratelli Foundation for Health Research and EducationRomeItaly
  4. 4.Laboratory of Neuroimmunology and Synaptic PlasticityIRCCS San Raffaele PisanaRomeItaly
  5. 5.Neuroimmunology Unit, Division of Neuroscience, Institute of Experimental Neurology (INSpe)San Raffaele Scientific InstituteMilanItaly

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