Assessment of Interleukin-37, the IL-37/TNF-α Ratio, and 8-OHdG as Novel Biomarkers of Oxidative Stress in Iraqi Patients with Hypothyroidism

Authors

DOI:

https://doi.org/10.23851/mjs.v37i3.1944

Keywords:

Hypothyroidism, Thyroxine, IL-37, 8-OHdG, Oxidative stress

Abstract

Background: Hypothyroidism is a commonly diagnosed endocrine disorder frequently associated with metabolic disturbances, oxidative stress, and immune dysfunction; growing evidence indicates that inflammation‑related cytokines and oxidative DNA damage contribute to disease progression even in patients receiving thyroid hormone replacement therapy. This study aimed to evaluate serum IL‑37 and TNF‑α and urinary 8‑OHdG levels and to assess the diagnostic and monitoring utility of the IL‑37/TNF‑α ratio by comparing these biomarkers across control, untreated hypothyroid, and post‑treatment groups. Objective: This study aims to examine the relationship between serum levels of IL-37, 8-OHdG, TNF-α, MDA, and the IL37/TNF-α ratio in patients with subclinical hypothyroidism. Methods: The study included 120 individuals divided into three groups: 30 newly diagnosed untreated patients, 30 patients receiving levothyroxine therapy, and 60 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum concentrations of IL-37, TNF-α, MDA, and 8-OHdG. Results: The results revealed that the levels of TNF-α, MDA, and 8-OHdG of the untreated hypothyroid group were significantly higher than those of both the treated and control groups. In contrast, IL-37 levels were significantly decreased, leading to a marked decrease in the IL-37/TNF-α ratio. The results exhibited significant improvement in inflammatory markers, with partial restoration of IL-37 levels and the IL-37/TNF-α ratio for those patients who are receiving levothyroxine therapy. In addition, MDA and 8-OHdG levels remained significantly higher in patients receiving levothyroxine than those observed in healthy controls. Conclusions: The findings indicate that, in hypothyroid subjects receiving prolonged hormone therapy, persistent oxidative DNA damage and elevated proinflammatory cytokine levels were observed. Measuring the levels of IL-37, 8-OHdG, and the IL-37/TNF-α ratio may be valuable adjunctive laboratory tests when assessing for inflammatory response, monitoring treatment effectiveness, and facilitating better insight into the underlying pathophysiologic mechanisms associated with subclinical hypothyroidism.

Downloads

Download data is not yet available.

References

L. Chaker and M. Papaleontiou, "Hypothyroidism: A review," JAMA, vol. 334, no. 19, pp. 1750-1760, 2025.

R. B. Bhandari and P. K. Mahto, "Effect of yoga therapy on hypothyroidism: A systematic review," Annals of Neurosciences, vol. 32, no. 3, pp. 207–218, 2024.

J. Li, Q. Huang, S. Sun, K. Zhou, X. Wang, K. Pan, Y. Zhang, Y. Wang, Q. Han, C. Si, et al., "Thyroid antibodies in Hashimoto's thyroiditis patients are positively associated with inflammation and multiple symptoms," Scientific Reports, vol. 14, no. 1, Art no. 27902, 2024.

V. A. Ranganath and I. Maity, "Artificial homeostasis systems based on feedback reaction networks: design principles and future promises," Angewandte Chemie, vol. 136, no. 14, Art no. e202318134, 2024.

L.-h. Chen, T. Xie, Q. Lei, Y.-r. Gu, and C.-z. Sun, "A review of complex hormone regulation in thyroid cancer: novel insights beyond the hypothalamus–pituitary–thyroid axis," Frontiers in Endocrinology, vol. 15, Art no. 1419913, Jul. 2024.

R. Sapin and J.-L. Schlienger, "Thyroxine (T4) and tri-iodothyronine (T3) determinations: techniques and value in the assessment of thyroid function," Annales de biologie clinique, vol. 61, no. 4, pp. 411–420, 2003, [Online] available. https://pubmed.ncbi.nlm.nih.gov/12915350/.

M. T. Macvanin, Z. Gluvic, S. Zafirovic, X. Gao, M. Essack, and E. R. Isenovic, "The protective role of nutritional antioxidants against oxidative stress in thyroid disorders," Frontiers in Endocrinology, vol. 13, Art no. 1092837, Jan. 2023.

Y. Qiu, Y. Hu, Z. Xing, Q. Fu, J. Zhu, and A. Su, "Birth control pills and risk of hypothyroidism: A cross-sectional study of the National Health and Nutrition Examination Survey, 2007-2012," BMJ Open, vol. 11, no. 6, Art no. e046607, 2021.

K. Fauci, H. Longo, and J. Loscalzo, Harrison’s principles of internal medicine. 1 vol. McGraw-Hill Book Company, 1988, [Online] available. https://books.google.iq/books?id=w62v0AEACAAJ.

U. M. Zamwar and K. N. Muneshwar, "Epidemiology, types, causes, clinical presentation, diagnosis, and treatment of hypothyroidism," Cureus, vol. 15, no. 9, Art no. e46241, 2023.

Z. Aleksic, A. Aleksic, and B. Djordjevic, "Subclinical hypothyroidism," Timočki Medicinski Glasnik, vol. 47, no. 1, pp. 11–23, 2022, [Online] available. https://tmg.org.rs/TMG–v4701e.pdf#page=11.

K. R. Riis, C. Larsen, B. R. Medici, C. Z. Jensen, K. H. Winther, E. L. Larsen, C. Ellervik, J. L. la Cour, L. Hegedus, T. H. Brix, et al., "Hypothyroid women have persistently higher oxidative stress compared to healthy controls," European Thyroid Journal, vol. 12, no. 6, Art no. e230167, 2023.

B. Biondi, F. S. Celi, and E. A. McAninch, "Critical approach to hypothyroid patients with persistent symptoms," The Journal of Clinical Endocrinology & Metabolism, vol. 108, no. 10, pp. 2708–2716, 2023.

M. Ishida, Hormone hunters: the discovery of adrenaline. Kyoto University Press, 2018, vol. 1, pp. 1–203.

S. Nilakanthan, K. Metri, N. Raghuram, and N. Hongasandra, "Effect of 6 months intense Yoga practice on lipid profile, thyroxine medication and serum TSH level in women suffering from hypothyroidism: A pilot study," Journal of Complementary and Integrative Medicine, vol. 13, no. 2, pp. 189–193, 2016.

K. Kubiak, M. K. Szmidt, J. Kaluza, A. Zylka, and E. Sicinska, "Do dietary supplements affect inflammation, oxidative stress, and antioxidant status in adults with hypothyroidism or Hashimoto's disease?—a systematic review of controlled trials," Antioxidants, vol. 12, no. 10, Art no. 1798, 2023.

F. Rada, "Inference of oxidative stress in patients with hypothyroidism," European Journal of Clinical and Experimental Medicine, vol. 22, no. 2, pp. 270–274, 2024.

R. Cordiano, M. Di Gioacchino, R. Mangifesta, C. Panzera, S. Gangemi, and P. L. Minciullo, "Malondialdehyde as a potential oxidative stress marker for allergy-oriented diseases: an update," Molecules, vol. 28, no. 16, Art no. 5979, 2023.

A. Goriuc, K.-A. Cojocaru, I. Luchian, R.-G. Ursu, O. Butnaru, and L. Foia, "Using 8-hydroxy-2'-Deoxiguanosine (8-OHdG) as a reliable biomarker for assessing periodontal disease associated with diabetes," International Journal of Molecular Sciences, vol. 25, no. 3, Art no. 1425, 2024.

K. D. Arczewska and A. Piekiełko-Witkowska, "The influence of micronutrients and environmental factors on thyroid DNA integrity," Nutrients, vol. 17, no. 13, Art no. 2065, 2025.

F. Mandal, S. K.C., S. R. Yadav, S. Kumar, P. K. Mishra, S. Shrestha, M. B. Khan, and R. K. Yadav, "Association between thyroid function and oxidative stress markers in overt and subclinical hypothyroid patients: observational cross-sectional study in Nepal," Palestinian Medical and Pharmaceutical Journal, vol. 10, no. 2, pp. 157–164, 2024.

S. Tahmasebi, M. Alimohammadi, S. Khorasani, and N. Rezaei, "Pro-tumorigenic and anti-tumorigenic roles of pro-inflammatory cytokines in cancer," in Cancer Immunology. Springer Nature Switzerland, 2025, vol. 1, pp. 529–553.

M. Gu, Y. Jin, X. Gao, W. Xia, T. Xu, and S. Pan, "Novel insights into IL-37: an anti-inflammatory cytokine with emerging roles in anti-cancer process," Frontiers in Immunology, vol. 14, Art no. 1278521, Oct. 2023.

B. Jiang, Y. Zhou, Y. Liu, S. He, B. Liao, T. Peng, L. Yao, and L. Qi, "Research progress on the role and mechanism of IL-37 in liver diseases," Seminars in Liver Disease, vol. 43, no. 3, pp. 336–350, 2023.

A. N. Syamsundara Kiran, G. K. Pal, P. Pal, S. Kamalanathan, S. Parija, and M. J. Pinjar, "Effects of six months of levothyroxine therapy on sympathovagal imbalance and cardiometabolic profile in overt hypothyroid patients," Cureus, vol. 17, no. 3, Art no. e81268, 2025.

B.-T. Zhang, M. Guo, L.-R. Yang, Y. Zeng, and J. Jiang, "Mechanistic aspects of inflammation and oxidative stress and their association with thyroid cancer risk," Cancer Medicine, vol. 14, no. 13, Art no. e71030, 2025.

J. Kaszycki and M. Kim, "Epigenetic regulation of transcription factors involved in NLRP3 inflammasome and NF-κB signaling pathways," Frontiers in Immunology, vol. 16, Art no. 1529756, Feb. 2025.

H. Zeng, K. Zhou, and Z. Ye, "Biology of interleukin-37 and its role in autoimmune diseases (review)," Experimental and Therapeutic Medicine, vol. 24, no. 2, Art no. 495, 2022.

L. T. Majnarić, Z. Bosnić, M. Štefanić, and T. Wittlinger, "Cross-Talk between the cytokine IL-37 and thyroid hormones in modulating chronic inflammation associated with target organ damage in age-related metabolic and vascular conditions," International Journal of Molecular Sciences, vol. 23, no. 12, Art no. 6456, 2022.

R. H. Jasim and W. M. Torki, "Interleukin-37 and Galectin-9: Suggested biochemical tools for diagnosis of untreated thyroidopathies," Pakistan Heart Journal, vol. 56, no. 3, pp. 1364–1373, 2023, [Online] available. https://www.pkheartjournal.com/index.php/journal/article/view/1873.

M. Fu, H. Wang, Y. Zhang, L. Yang, Y. Chen, X. Chen, Z. Wang, and H. Sun, "Thyroid stimulating hormone may facilitates adipose tissue insulin resistance by inducing M1 macrophage polarization," Journal of Inflammation Research, vol. 18, pp. 8331–8343, Jun. 2025.

Bushra, S. Kapoor, and T. Mahmood, "Study of oxidative stress and inflammatory status in thyroid dysfunction: a systematic review," International Journal of Drug Delivery Technology, vol. 14, no. 1, pp. 515–522, 2024.

F. Orrico, S. Laurance, A. C. Lopez, S. D. Lefevre, L. Thomson, M. N. Möller, and M. A. Ostuni, "Oxidative stress in healthy and pathological red blood cells," Biomolecules, vol. 13, no. 8, Art no. 1262, 2023.

R. M. Jasim and A. M. N. Jassim, "Evaluation of MDA and serum minerals in patients with overt and subclinical hypothyroidism," International Journal of Health Sciences, vol. 6, no. S5, pp. 4773–4784, 2022.

S. Panda, O. Chatterjee, G. Mukherjee, and S. Chatterjee, "Human diseases induced by oxidative damage in DNA," in Nucleic Acid Biology and its Application in Human Diseases. Springer Nature Singapore, 2023, pp. 135–166.

K. D. Arczewska, D. Sys, H. L. Nilsen, and A. Piekiełko-Witkowska, "DNA damage and repair in thyroid physiology and disease," Endocrine Reviews, vol. 47, no. 1, pp. 121–157, 2025.

S. G. Dragoev, "Lipid peroxidation in muscle foods: impact on quality, safety and human health," Foods, vol. 13, no. 5, Art no. 797, 2024.

J. Hidalgo, B. A. Vallejo, C. Soto Jacome, I. N. Ayala, S. Cordova, M. Duran, E. Golembiewski, D. Toro-Tobon, and J. P. Brito, "Real practice assessment of persistent symptoms after initiation of levothyroxine," Endocrine Practice, vol. 30, no. 2, pp. 95–100, 2024.

M. Freeman, G. A. Adunlin, C. Mercadel, S. Danzi, and I. Klein, "Hypothyroid symptoms in levothyroxine-treated patients," INNOVATIONS in pharmacy, vol. 10, no. 3, Art no. 19, 2019.

P. Perros, C. Van Der Feltz-Cornelis, E. Papini, E. V. Nagy, A. P. Weetman, and L. Hegedüs, "The enigma of persistent symptoms in hypothyroid patients treated with levothyroxine: A narrative review," Clinical Endocrinology, vol. 98, no. 4, pp. 461–468, 2021.

1944.image

Downloads

Key Dates

Received

04-07-2026

Revised

04-09-2026

Accepted

07-09-2026

Published

30-09-2026

Data Availability Statement

Data are available from the authors upon reasonable request.

Issue

Section

Original Article

How to Cite

[1]
A. A. Hammed and F. S. Al-Fartusie, “Assessment of Interleukin-37, the IL-37/TNF-α Ratio, and 8-OHdG as Novel Biomarkers of Oxidative Stress in Iraqi Patients with Hypothyroidism”, Al-Mustansiriyah J. Sci., vol. 37, no. 3, pp. 48–58, Sep. 2026, doi: 10.23851/mjs.v37i3.1944.

Similar Articles

41-50 of 317

You may also start an advanced similarity search for this article.