Impact of Low Interferon-γ and IL-10 Levels on TNF-α and IL-6 Production by PHA-Induced PBMCs in Type 2 Diabetes Mellitus

• Published in: Journal of inflammation research 2020-01, Vol.13, p.187-193
• Main Authors: Kartika, Rona, Purnamasari, Dyah, Pradipta, Saraswati, Larasati, Rahma A, Wibowo, Heri
• Format: Article
• Language: English
• Subjects: Centrifugation; Cytokines; Diabetes; Diabetes mellitus (non-insulin dependent); Immune response; Inflammation; Insulin; Interferon; Interleukin 10; Interleukin 6; Laboratories; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Monocytes; Original Research; Pathogenesis; Peripheral blood mononuclear cells; proinflammatory response; Statistical analysis; Tumor necrosis factor-TNF; Tumor necrosis factor-α; type 2 diabetes mellitus; γ-Interferon
• ISSN: 1178-7031; 1178-7031
• DOI: 10.2147/JIR.S245064

In this study, we analyzed the production of interferon γ (IFN-γ) and interleukin 10 (IL-10) by peripheral blood mononuclear cells (PBMCs) in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the capacity of monocytes to produce tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) following IFN-γ stimulation and the associated role of IL-10 in TNF-α and IL-6 production. In vitro experiments were conducted on PBMCs obtained from 19 patients with T2DM and 17 healthy participants. PBMCs were isolated from venous blood by density gradient centrifugation, followed by 3-day phytohemagglutinin induction. In vitro production of TNF-α, IL-6, IFN-γ, and IL-10 was measured using the multiplex immunoassay. Statistical analysis was performed using IBM SPSS 23 version. IFN-γ concentration in the T2DM group was significantly lower than that in control group (T2DM 7,700.86 ± 3,037.77 vs control 10,672.69 ± 5,625.50 pg/mL; = 0.048). However, TNF-α, IL-6, and IL-10 levels showed no significant difference between the two groups. The TNF-α/IFN-γ and IL-6/IFN-γ ratios were significantly higher in T2DM than in the control group ( = 0.026 and = 0.048, respectively). In T2DM, the high TNF-α/IFN-γ ratio was consistent, with the low baseline IL-10 level ( = 0.022). In T2DM, T-cell response is impaired with significantly reduced IFN-γ production, and simultaneously, circulatory monocytes show enhanced cellular responsiveness to inflammatory stimuli. The low baseline IL-10 level likely contributes to such an immune response.