The alterations of cerebrospinal fluid TNF-alpha and TGF-beta2 levels in early relapsing-remitting multiple sclerosis

Immunol Res. 2022 Oct;70(5):708-713. doi: 10.1007/s12026-022-09303-x. Epub 2022 Jun 21.

Abstract

Aim of the study: This study aimed to analyze serum and cerebrospinal fluid (CSF) concentrations of proinflammatory and anti-inflammatory cytokines produced by T regulatory (Treg) cells in early RRMS according to the 2017 McDonald criteria.

Clinical rationale for the study: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) with the cytokine network playing an important role. However, there is a continual lack of data regarding the immunopathogenesis of early RRMS, especially according to the 2017 McDonald criteria.

Materials and methods: The study groups included early RRMS patients during relapse (n = 18), remission (n = 14), and the control group. The MS diagnosis was established according to the 2017 McDonald criteria. Patients were studied up to 1 year after diagnosis was made. A quantitative test kit based on ELISA was used for cytokine measurement in the serum and CSF. Comparative and correlation analyses between the levels of TNF-α, TGF-β2, IgG index, and relapse duration were performed.

Results: Significantly higher CSF concentrations of TNF-α in both RRMS-relapse and RRMS-remission groups were found compared to the controls (p < 0.01). The CSF levels of TGF-β2 in the RRMS-relapse group were significantly lower in comparison to the control group (p = 0.01).

Conclusions and clinical implications: An inappropriate inflammatory response seems to occur in early RRMS and includes the production of TNF-α and a decrease in TGF-β2 release suggesting a significant Treg cells role. Further studies on the topic may contribute to developing new disease-modifying drugs and biochemical markers of the disorder.

Keywords: Cerebrospinal fluid; Cytokine; Multiple sclerosis; Relapsing–remitting; TGF–beta; TNF–alpha; Treg cell.

MeSH terms

  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cytokines
  • Humans
  • Immunoglobulin G
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis, Relapsing-Remitting* / blood
  • Multiple Sclerosis, Relapsing-Remitting* / cerebrospinal fluid
  • Multiple Sclerosis, Relapsing-Remitting* / immunology
  • Recurrence
  • Transforming Growth Factor beta2* / blood
  • Transforming Growth Factor beta2* / cerebrospinal fluid
  • Transforming Growth Factor beta2* / immunology
  • Tumor Necrosis Factor-alpha* / blood
  • Tumor Necrosis Factor-alpha* / cerebrospinal fluid
  • Tumor Necrosis Factor-alpha* / immunology

Substances

  • Biomarkers
  • Cytokines
  • Immunoglobulin G
  • TGFB2 protein, human
  • TNF protein, human
  • Transforming Growth Factor beta2
  • Tumor Necrosis Factor-alpha