Role of Pro-Inflammatory Cytokines and Biochemical Markers in the Pathogenesis of Type 1 Diabetes: Correlation with Age and Glycemic Condition in Diabetic Human Subjects

PLoS One. 2016 Aug 30;11(8):e0161548. doi: 10.1371/journal.pone.0161548. eCollection 2016.

Abstract

Background: Type 1 diabetes mellitus is a chronic inflammatory disease involving insulin producing β-cells destroyed by the conjoined action of auto reactive T-cells, inflammatory cytokines and monocytic cells. The aim of this study was to elucidate the status of pro-inflammatory cytokines and biochemical markers and possible correlation of these factors towards outcome of the disease.

Methods: The study was carried out on 29 T1D subjects and 20 healthy subjects. Plasma levels of oxidative stress markers, enzymatic and non-enzymatic antioxidants were estimated employing biochemical assays. The levels of pro-inflammatory cytokines such as by IL-1β & IL-17 in the serum were determined by ELISA, while the expression of TNF-α, IL-23 & IFN-γ was ascertained by qRT-PCR.

Results: The onset of T1D disease was accompanied with elevation in levels of Plasma malondialdehyde, protein carbonyl content and nitric oxide while plasma vitamin C, reduced glutathione and erythrocyte sulfhydryl groups were found to be significantly decreased in T1D patients as compared to healthy control subjects. Activity of antioxidant enzymes, superoxide dismutase, catalase, glutathione reductase and glutathione-s-transferase showed a significant suppression in the erythrocytes of T1D patients as compared to healthy subjects. Nevertheless, the levels of pro-inflammatory cytokines IL-1β and IL-17A were significantly augmented (***p≤.001) on one hand, while expression of T cell based cytokines IFN-γ, TNF-α and IL-23 was also up-regulated (*p≤.05) as compared to healthy human subjects.

Conclusion: The level of pro-inflammatory cytokines and specific biochemical markers in the serum of the patient can be exploited as potential markers for type 1 diabetes pathogenesis. The study suggests that level of inflammatory markers is up-regulated in T1D patients in an age dependent manner.

MeSH terms

  • Adolescent
  • Age Factors
  • Biomarkers / blood*
  • Child
  • Cytokines / blood*
  • Cytokines / genetics*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / metabolism*
  • Female
  • Humans
  • Male
  • Malondialdehyde / blood
  • Nitric Oxide / blood
  • Oxidative Stress
  • Protein Carbonylation
  • Up-Regulation
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • Nitric Oxide
  • Malondialdehyde

Grants and funding

This work was supported in part by the Department of Biotechnology, Govt. of India, through a Senior Research Fellowship grant (SRF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.