Trans-signaling through the agonistic sIL-6R and an imbalanced inflammatory response are associated with increased susceptibility to Graves’ disease; [La trans-señalización a través del receptor agonista sIL-6R y la respuesta inflamatoria desequilibrada están asociadas con la predisposición a la enfermedad de Graves]

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Zulvikar Syambani Ulhaq, Zulkarnain Zulkarnain, Lola Ayu Istifiani, Syafrizal Aji Pamungkas, Susiati, Djoko Wahono Soeatmadji, Aulanni'am Aulanni'am

2025 Endocrinologia, Diabetes y Nutricion Vol. 72 Issue 7 Article Cited by 1 Quartile

Abstract

Background: Excessive inflammatory cytokines are known to impact immune response and autoimmunity. In this study, we quantified the level of interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), glycoprotein 130 (sgp130) and IL-10 to determine their involvement in the pathogenesis of Graves’ disease (GD), in addition to the assessment serum cytokines IL-6, sIL-6R, sgp130, and IL-10 performance as biomarkers for the diagnosis of GD. Methods: A total of 20 patients with GD and 21 healthy individuals from the Indonesian population were enrolled. The serum concentrations of the selected cytokines were quantified using the ELISA method. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and TSH receptor antibody (TSHR-Ab) were also evaluated. Comparative analysis was performed in addition to the assessment of the diagnostic performance of cytokines using receiver-operating-curve (ROC) analysis. Pearson's correlation coefficient was used to assess the relationship between 2 quantitative variables. Results: Patients with GD had a higher IL-6, sIL-6R, and IL-6/IL-10 ratio but a lower sgp130/sIL-6R/IL-6 ratio vs controls. The ROC curve analysis showed that the sgp130/sIL-6R/IL-6 ratio exhibited better performance than IL-6, sIL-6R, and IL-6/IL-10 ratio in diagnosing GD. In addition, serum levels of IL-6, sIL-6, and IL-10 were associated with thyroid parameters, including TSHR-antibody (Ab) levels. Conclusion: IL-6 trans-signaling and imbalance of inflammatory response could be prominent factors in the pathogenesis of GD. © 2025 SEEN y SED

Affiliations

Research Center for Pre-clinical and Clinical Medicine, National Research and Innovation Agency Republic of Indonesia, Cibinong 16911, Indonesia; Department of Physiology, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh 23111, Indonesia; Department of Nutrition, Faculty of Health Sciences, Universitas Brawijaya, Malang 65151, Indonesia; Department of Periodontics, Faculty of Dentistry, Universitas Airlangga, Surabaya 60132, Indonesia; Directorate of Innovation and Science & Technology Area (DIKST) Universitas Brawijaya, Malang 65145, Indonesia; Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang 65145, Indonesia; Department of Chemistry, Faculty of Science, Universitas Brawijaya, Malang 65145, Indonesia