Profiling of Canonical and Non-Traditional Cytokine Levels in Interferon-β-Treated Relapsing-Remitting-Multiple Sclerosis Patients

Front Immunol. 2018 Jun 4:9:1240. doi: 10.3389/fimmu.2018.01240. eCollection 2018.


Background: Multiple sclerosis (MS) is a chronic, progressive autoimmune disease of the central nervous system in which inflammation plays a key role in the induction, development, and progression. Most of the MS patients present with relapsing-remitting (RR) form, characterized by flare-ups followed by periods of recovery. Many inflammatory and anti-inflammatory cytokines have been proposed as backers in MS pathogenesis, and the balance between these differing cytokines can regulate MS severity. Interferon (IFN)-β, a current disease-modifying therapy for MS, has demonstrated beneficial effects in reducing disease severity in MS patients. However, its immunoregulatory and anti-inflammatory actions in MS are not wholly understood. The aim of the study was to define, in clinically stable patients with RR-MS, the serum concentration of several cytokines, canonical or not, and their modulation by IFN-β therapy.

Methods: Relapsing-remitting-MS patients were enrolled and diagnosed according to revised Mc Donald Diagnostic Criteria. A set of cytokines [including non-canonical neurotransmitter acetylcholine (ACh) and adipokines] and B-cell differentiation molecules, as potential biomarkers, were evaluated in 30 non-treated RR-MS patients compared to 30 IFN-β-treated MS patients and 30 age, gender, and body mass index-matched healthy controls (HC).

Results: Naïve MS patients showed significantly higher levels of interleukin (IL)-1β, IL-12/IL-23p40, IL-18, high-mobility group box protein-1, and IL-18 binding protein (IL-18BP) than MS-treated patients (p < 0.001 for all) and HC (p < 0.01). IFN-β therapy has significantly downmodulated IL-1β, IL-12/IL-23p40, IL-18 to normal levels (p < 0.001), whereas it has decreased IL-18BP (p < 0.001). ACh was significantly higher in the IFN-β-treated than HC and non-treated MS patients (p < 0.001). No significant differences were observed either in adipokines concentration or in B-cell-associated molecules among the three study groups.

Conclusion: Although more experimental evidence are required, we speculate that the efficacy of treatment of MS with IFN-β is mediated, at least in part, by its ability to work on several levels to slow down the disease progression. Proposed actions include the modulation of IL-1-inflammasome axis and modulation of ACh, B-cell activating factor/a proliferation-inducing ligand system, and several adipokines.

Keywords: adipokines; inflammasome; interferon-β therapy; multiple sclerosis; pro-inflammatory cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers*
  • Case-Control Studies
  • Cytokines / blood*
  • Disabled Persons
  • Female
  • Humans
  • Inflammasomes
  • Inflammation Mediators / metabolism
  • Interferon-beta / therapeutic use
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / blood*
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis
  • Multiple Sclerosis, Relapsing-Remitting / therapy
  • Severity of Illness Index


  • Biomarkers
  • Cytokines
  • Inflammasomes
  • Inflammation Mediators
  • Interferon-beta