Interferon beta treatment of multiple sclerosis increases serum interleukin-7

Mult Scler. 2014 Nov;20(13):1727-36. doi: 10.1177/1352458514532700. Epub 2014 May 12.

Abstract

Background: Interleukin-7 (IL-7) is a non-redundant cytokine for T-cell development and survival. The IL-7 signaling pathway has been genetically and functionally associated with several autoimmune diseases including multiple sclerosis (MS).

Objective: The objective of this paper is to elucidate the effect of the widely used immunomodulatory MS therapy interferon beta (IFNβ) on IL-7 homeostasis.

Methods: Swedish MS patients were screened for IL-7 concentration in serum and blood cell counts. IL-7 receptor alpha chain (IL-7Rα) expression was determined by semi-quantitative real-time polymerase chain reaction (PCR) and flow cytometry.

Results: IFNβ treatment led to significantly increased serum IL-7 levels (mean: 17 pg/ml) compared with healthy controls (mean: 7.6 pg/ml) and natalizumab-treated patients (mean: 5.3 pg/ml). In vitro and in vivo, peripheral blood leukocytes showed decreased IL-7Rα expression and IL-7 consumption upon IFNβ exposure, suggesting that their IL-7 responsiveness is impaired during treatment.

Conclusions: MS patients undergoing IFNβ treatment have increased serum IL-7 levels and decreased IL-7 consumption. Given IL-7's important role in T-cell immunity, this relationship may be highly relevant for IFNβ's treatment efficacy.

Keywords: Multiple sclerosis; immunology; interferon beta; natalizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interferon-beta / therapeutic use*
  • Interleukin-7 / blood*
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Real-Time Polymerase Chain Reaction
  • Receptors, Interleukin-7 / blood
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Neutralizing
  • IL7 protein, human
  • Immunosuppressive Agents
  • Interleukin-7
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain
  • Interferon-beta