Increased pro-inflammatory cytokine gene expression in peripheral blood mononuclear cells of patients with polyneuropathies

J Neurol. 2018 Mar;265(3):618-627. doi: 10.1007/s00415-018-8748-4. Epub 2018 Jan 25.

Abstract

Background: Distinct cytokine expression patterns have been reported in biomaterial of patients with polyneuropathies (PNP). We investigated gene expression profiles of pro- and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMC) of patients with neuropathies of different etiologies.

Methods: We prospectively studied 97 patients with neuropathies and compared data between diagnostic subgroups and healthy controls. Gene expression of a panel of pro- and anti-inflammatory cytokines was analyzed (interleukin-1 [IL-1], IL-2, IL-6, IL-8, tumor necrosis factor alpha [TNF], IL-4, and IL-10) in PBMC samples. Furthermore, protein levels of IL-6, IL-8, and TNF were measured in supernatant of PBMC stimulated with lipopolysaccharide (LPS).

Results: PNP were associated with higher PBMC gene expression of IL-1 (p < 0.05), IL-2 (p < 0.05), IL-8 (p < 0.001), and TNF (p < 0.01) compared to healthy controls. Inflammatory neuropathies were associated with higher gene expression of IL-8 (p < 0.001) and TNF (p < 0.05) and lower gene expression of IL-10 (p < 0.05) compared to healthy controls. More pro-inflammatory cytokines were elevated in painful neuropathy (IL-1, IL-2 [p < 0.05], IL-8 [p < 0.001] and TNF [p < 0.05]) than in painless neuropathy (IL-8 [p < 0.01] and TNF [p < 0.01]) compared to healthy controls, while IL-10 expression was higher in treatment naïve patients with painless neuropathy compared to patients with painful neuropathy (p < 0.05). Disease duration positively correlated with IL-6 gene expression (p < 0.01). Supernatant protein levels of IL-6, IL-8, and TNF did not differ between groups.

Conclusion: Systemic gene expression of pro-inflammatory cytokines is increased in patients with neuropathies and may be influenced by the presence of neuropathic pain.

Keywords: Cytokine; Gene expression; Neuropathic pain; Peripheral blood mononuclear cells; Peripheral neuropathy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cytokines / blood*
  • Female
  • Gene Expression
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Lipopolysaccharides
  • Male
  • Middle Aged
  • Neuralgia / blood
  • Neuralgia / immunology
  • Polyneuropathies / blood*
  • Polyneuropathies / immunology*
  • Prospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult

Substances

  • Cytokines
  • Lipopolysaccharides