Monocyte and Lymphocyte Activation and Regulation in Multiple Sclerosis Patients. Therapy Effects

J Neuroimmune Pharmacol. 2019 Sep;14(3):413-422. doi: 10.1007/s11481-018-09832-z. Epub 2019 Jan 16.

Abstract

Analysis of gut barrier status, monocyte and lymphocyte activation and T regulatory (Treg) cells at diagnosis before and after therapy, in patients with multiple sclerosis (MS). Analysis of differential effects of interferon beta (IFN-β), glatiramer acetate (GA) and natalizumab. Thirty-five patients with untreated MS were included. Gut barrier status (serum concentrations of intestinal fatty acid binding protein), monocyte (serum levels of soluble CD14, soluble CD163 and interleukin 6) and T lymphocyte activation (CD4 + DR+ and CD8 + DR+) and Treg (CD4 + CD25highFoxP3+) cells were analyzed. Patients with clinical isolated syndrome and relapsing-remitting forms were treated with IFN-β or GA, and immune characteristics were reevaluated following up after 6 months. A sample of 56 stable RR MS patients, in treatment with IFN-β, GA or natalizumab, and 50 healthy individuals were included as controls. Gut barrier status was similar in MS patients and healthy controls. Untreated patients with relapsing-remitting and primary progressive patterns of MS showed increased serum levels of soluble CD14. At baseline, significant increases in activated T lymphocytes and Treg were detected in patients. A significant decrease of CD4 + DR+, CD8 + DR+, and Treg percentages after 6 months of therapy was observed. In previously treated patients, IFN-β, GA, or natalizumab therapies were associated with a comparable cell proportion of activated lymphocytes and Treg. MS patients have a baseline state characterized by monocyte and lymphocyte activation, not related with gut barrier lesion. An increase in Treg number, correlated with activated T CD8+ lymphocytes, was detected. Treatment with IFN-β, GA or natalizumab was associated with a comparable decrease in activated lymphocytes and Treg. Graphical Abstract ᅟ.

Keywords: Activated T lymphocytes; Gut barrier permeability; Interleukin 6; Multiple sclerosis; T regulatory cells; sCD14; sCD163.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Fatty Acid-Binding Proteins / blood
  • Female
  • Gene Expression Regulation / drug effects
  • Glatiramer Acetate / pharmacology*
  • Glatiramer Acetate / therapeutic use
  • Humans
  • Interferon-beta / pharmacology*
  • Interferon-beta / therapeutic use
  • Lymphocyte Activation / drug effects*
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / metabolism
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis, Chronic Progressive / drug therapy*
  • Multiple Sclerosis, Chronic Progressive / immunology
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • NF-kappa B / metabolism
  • Natalizumab / pharmacology*
  • Natalizumab / therapeutic use
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Prospective Studies
  • Signal Transduction / drug effects
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Fatty Acid-Binding Proteins
  • NF-kappa B
  • Natalizumab
  • Nerve Tissue Proteins
  • Glatiramer Acetate
  • Interferon-beta