Dysregulation of the IL-23/IL-17 axis and myeloid factors in secondary progressive MS

Neurology. 2014 Oct 21;83(17):1500-7. doi: 10.1212/WNL.0000000000000908. Epub 2014 Sep 24.


Objective: In the current exploratory study, we longitudinally measured immune parameters in the blood of individuals with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), and investigated their relationship to disease duration and clinical and radiologic measures of CNS injury.

Methods: Peripheral blood mononuclear cells (PBMCs) and plasma were obtained from subjects with RRMS, SPMS, and from healthy controls on a monthly basis over the course of 1 year. MRI and Expanded Disability Status Scale evaluations were performed serially. PBMCs were analyzed by enzyme-linked immunosorbent spot assay to enumerate myelin basic protein-specific interleukin (IL)-17- and interferon (IFN)-γ-producing cells. Plasma concentrations of proinflammatory factors were measured using customized Luminex panels.

Results: Frequencies of myelin basic protein-specific IL-17- and IFN-γ-producing PBMCs were higher in individuals with RRMS and SPMS compared to healthy controls. Patients with SPMS expressed elevated levels of IL-17-inducible chemokines that activate and recruit myeloid cells. In the cohort of patients with SPMS without inflammatory activity, upregulation of myeloid-related factors correlated directly with MRI T2 lesion burden and inversely with brain parenchymal tissue volume.

Conclusions: The results of this exploratory study raise the possibility that Th17 responses and IL-17-inducible myeloid factors are elevated during SPMS compared with RRMS, and correlate with lesion burden. Our data endorse further investigation of Th17- and myeloid-related factors as candidate therapeutic targets in SPMS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cytokines / blood*
  • Disability Evaluation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interleukin-17 / blood
  • Interleukin-23 / blood
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / pathology
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / blood*
  • Multiple Sclerosis, Chronic Progressive / pathology*
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Myelin Basic Protein / blood*


  • Cytokines
  • Interleukin-17
  • Interleukin-23
  • Myelin Basic Protein
  • Interferon-gamma