Elevated Levels of T-helper 17-associated Cytokines in Diabetes Type I Patients: Indicators for Following the Course of Disease

Immunol Invest. 2016 Oct;45(7):641-51. doi: 10.1080/08820139.2016.1197243. Epub 2016 Sep 9.

Abstract

Background: Type 1 diabetes (T1D) is thought to involve chronic inflammation, which is manifested by the activation and expression of different inflammatory mediators. Th1- and Th17-associated cytokines are factors that have been shown to exert profound pro-inflammatory activities and have been implicated in the pathogenesis of T1D in mice and humans.

Objectives: Therefore, the aim of this case control study was to determine the serum level of IL-17, IL-21, IL-27, transforming growth factor beta (TGF-β), and IFN-γ and their reciprocal relationship in Iranian T1D patients.

Patients and methods: Blood samples were collected from 48 T1D patients and 49 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling. The serum levels of IL-17, IL-21, IL-27, TGF-β, and IFN-γ were measured by the enzyme linked immunosorbent assay (ELISA).

Results: The serum levels of IL-17 and IL-21 were significantly higher in T1D patients compared to the healthy individuals (p = 0.005 and 0.01, respectively), but interestingly, the opposite was the case for IL-27 (p < 0.0001). However, there were no significant differences in TGF-β and IFN-γ between both groups. In addition, IL-17/IFN-γ and IL-17/IL-27 ratios were higher in patients compared to the control group.

Conclusions: Our results indicated dominant Th17-associated IL-17, suggesting a shift from the Treg and Th1 phenotypes toward the Th17 phenotype. Therefore, it can promote inflammation in β cells in T1D. In addition, it suggests the role of Th17 and Th17/Th1 ratios as a potential contributor to β cells destruction and the Th17/Th1 response ratio may provide a novel biomarker for rapid T1D diagnosis before the destruction of β cells and progression of the disease to the clinical end stages.

Keywords: Diabetes type 1; Interferon gamma; Interleukin-17; Interleukin-21; Interleukin-27; transforming growth factor beta.

MeSH terms

  • Adolescent
  • Animals
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Humans
  • Inflammation / immunology*
  • Interferon-gamma / blood
  • Interleukin-17 / blood*
  • Interleukins / blood*
  • Iran
  • Male
  • Mice
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*
  • Transforming Growth Factor beta / blood
  • Young Adult

Substances

  • IL17A protein, human
  • Interleukin-17
  • Interleukins
  • MYDGF protein, human
  • Transforming Growth Factor beta
  • Interferon-gamma
  • interleukin-21