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
Received 9 January 2020
Accepted for publication 7 April 2020
Published 22 April 2020 Volume 2020:13 Pages 187—193
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Ning Quan
Rona Kartika,1 Dyah Purnamasari,2 Saraswati Pradipta,1 Rahma A Larasati,3 Heri Wibowo4
1Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia; 2Division of Metabolic Endocrinology and Diabetes, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia; 3Department of Biomedicines, Faculty of Medicine, Universitas Muhammadiyah Jakarta, Jakarta, Indonesia; 4Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
Correspondence: Heri Wibowo
Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
Purpose: 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.
Patients and Methods: 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.
Results: 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; p = 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 (p = 0.026 and p = 0.048, respectively). In T2DM, the high TNF-α/IFN-γ ratio was consistent, with the low baseline IL-10 level (p = 0.022).
Conclusion: 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.
Keywords: type 2 diabetes mellitus, proinflammatory response, cytokines
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