T Helper 1 Cytokines and Their Relationship with Beta Cell Function in Type 1 Diabetes

Abstract

Objective: In type 1 diabetes (T1D), T helper (Th) 1 cells affect β cell functions significantly. This study aims to explore the association between serum levels of Th1 cytokines [interferon-gamma (IFN-γ), interleukin (IL)-2 and tumor necrosis factor-alpha (TNF-α)] and β cell function in T1D. Material and Methods: The study included 110 patients with T1D (TIDPs) and 31 healthy controls. The β cell functions in T1DPS were assessed by calculating mixed-meal stimulated C-peptide levels. T1DPs were categorized into three groups depending on results of this test (1a-lowest, 1b, 1chighest). Cytokine levels, IFN-γ/IL-2, and TNF-α/IL-2 ratios in T1DPs were compared with that in controls. Correlation analysis between cytokine levels and diabetes-related parameters was then carried out. Results: IFN-γ, TNF-α, IL-2 levels, and TNF-α/IL-2 of T1DPs were higher (p=0.02, p=0.01, p=0.008, and p=0.01, respectively) than that of controls. The highest IFN-γ/IL-2 and TNF-α/IL-2 ratios were observed in group 1b (p=0.03 and p=0.04, respectively) while the lowest IFN-γ/IL-2 and TNF-α/IL-2 ratios were observed in group 1a (p=0.03 and p=0.04, respectively). The TNF-α levels were found to be negatively correlated with fasting glucose levels (r 2 =-0.003, p=0.031). However, after adjustment for age and gender, this correlation diminished (r 2 =-0.028, p=0.076). Conclusion: IFN-γ, IL-2, and TNF-α may exhibit a triggering role in the pathogenesis of T1D. IFN-γ/IL-2 and TNF-α/IL-2 ratios possibly have more significant roles in the progression of β cell dysfunction than other cytokines (Clini-calTrials.gov number: NCT02389335).