Evaluation of Pro- and Anti-inflammatory Cytokines IL-17 and IL-33 in Autoimmune Hyperthyroidism-Scilight

Trends in Immunotherapy

Article

Evaluation of Pro- and Anti-inflammatory Cytokines IL-17 and IL-33 in Autoimmune Hyperthyroidism

Downloads

Mahdi, M. F., & Abdulkhaliq, R. J. (2025). Evaluation of Pro- and Anti-inflammatory Cytokines IL-17 and IL-33 in Autoimmune Hyperthyroidism. Trends in Immunotherapy, 9(3), 140–150. https://doi.org/10.54963/ti.v9i3.1164

Authors

  • Malak Fadel Mahdi

    National Center of Hematology, Mustansiriyah University, 10052, Baghdad, Iraq
  • Roua Jamal Abdulkhaliq

    Department of Pathological Analysis, Collage of Applied Science, University of Fallujah, 31002 Al‑Anbar, Iraq

Received: 15 April 2025; Revised: 11 June 2025; Accepted: 23 June 2025; Published: 15 August 2025

Hyperthyroidism is a medical condition characterized by the excessive production and release of thyroid hormones by the thyroid gland. It has diverse etiologies, clinical manifestations, and treatment options. Among the contributing factors to the development of thyroid disease are cytokines, which influence both the immune system and thyroid follicular cells. Notably, cytokines such as IL-17 and IL-33 play critical roles in autoimmune thyroid diseases by promoting inflammation and modulating immune responses. This study aimed to evaluate the serum levels of IL-17 and IL-33 in Iraqi individuals diagnosed with hyperthyroidism. A total of  60 hyperthyroid patients (21 males and 39 females, aged 17–40 years) and 30 healthy controls (8 males and 22 females) were enrolled. Blood samples were collected, and serum levels of IL-17 and IL-33 were measured using standard ELISA techniques. The results demonstrated a statistically significant increase in IL-17 concentrations in patients with hyperthyroidism (39.480 ± 9.665 ng/L) compared to controls (25.695 ± 4.448 ng/L) (p ≤ 0.01). Similarly, IL-33 levels were significantly elevated in the patient group (1247.745 ± 966.963 ng/L) compared to the control group (32.788 ± 47.741 ng/L) (p ≤ 0.01). These findings suggest a potential role for IL-17 and IL-33 in the immunopathogenesis of hyperthyroidism, highlighting their value as possible biomarkers for disease progression.

Keywords:

Autoimmune Disorder Inflammation Graves’ Disease Cytokines Thyroid‑Stimulating Hormone

References

  1. Kostopoulos, G.; Effraimidis, G. Epidemiology, Prognosis, and Challenges in the Management of Hyperthyroidism-Related Atrial Fibrillation. Eur. Thyroid J. 2024, 13.
  2. Yeza, E.N.G.; Mir, C.N.; Ares, R.M.; et al. Prevalence of Thyroid Dysfunction and Its Relationship with the Lipid Profile in Patients at the Hospital of Encarnación. Rev. Cienc. Tecnol. (RECyT) 2021, 36, 70–77.
  3. Wiersinga, W.M.; Poppe, K.G.; Effraimidis, G. Hyperthyroidism: Aetiology, Pathogenesis, Diagnosis, Management, Complications, and Prognosis. Lancet Diabetes Endocrinol. 2023, 11, 282–298.
  4. Th, S., & Sh, I. (2024). IL_33 as a Modulator of Neuroinflammation in Alzheimer’s disease: An ELISA Approach. Al-Turath Medical Journal, 1(1), 1-10.‏
  5. Rudijanto, A.; Wijaya, A.B. Advances in Thyroid Peroxidase (TPO) and Thyroid-Stimulating Hormone Receptor (TSHR) Biomarkers for Autoimmune Thyroid Diseases. Acta Biochim. Indones. 2024, 7, 182.
  6. Li, M.; Yang, X.; Li, R.; et al. Visceral Fat Area and Subcutaneous Fat Area Increase in Hyperthyroidism Patients After Treatment: A Single-Group Repeated-Measures Trial. Diabetes Metab. Syndr. Obes. 2024, 17, 2165–2176.
  7. Weaver, D.F. Amyloid‐β Is a Cytokine. Alzheimers Dement. 2023, 19, 4237–4247.
  8. Th, S., & Sh, I. (2024). Exploring IL_18 Levels in Alzheimer’s disease progression Using ELISA Methodology. Al-Turath Medical Journal, 1(1), 11-20.‏
  9. Li, S.; Li, S.; Lin, M.; et al. Interleukin-17 and Vascular Endothelial Growth Factor: New Biomarkers for the Diagnosis of Papillary Thyroid Carcinoma in Patients with Hashimoto's Thyroiditis. J. Int. Med. Res. 2022, 50, 03000605211067121.
  10. Li, M.; Chi, X.; Wang, Y.; et al. Trends in Insulin Resistance: Insights into Mechanisms and Therapeutic Strategy. Signal Transduct. Target. Ther. 2022, 7, 216.
  11. Bayraktar, N.; Eren, M.A.; Bayraktar, M.; et al. Analysis of Interleukin-17, Interleukin-23, Neopterin and Nesfatin-1 Levels in the Sera of Hashimoto Patients. J. Med. Biochem. 2023, 42, 460.
  12. Saad, K.A.; Tektook, N.K.; Threaf, M.F. Interleukin-17, IL-18, and IL-22 Levels in Autoimmune Thyroid Disease and Polycystic Ovary Syndrome. Health Sci. Bull. 2022, 140, 1897–1903.
  13. Nafh, S.A.; Al-Jumaily, R.M.K. Effect of Radioactive Iodine Therapy on Interleukin-2 (IL-2), IL-17, and Physiological Parameters in Iraqi Patients with Graves' Disease. Egypt. J. Hosp. Med. 2023, 90, 3636–3640.
  14. De Boeck, A.; Ahn, B.Y.; D’Mello, C.; et al. Glioma-Derived IL-33 Orchestrates an Inflammatory Brain Tumor Microenvironment That Accelerates Glioma Progression. Nat. Commun. 2020, 11, 4997.
  15. Cayrol, C.; Girard, J.P. Interleukin‐33 (IL‐33): A Nuclear Cytokine from the IL‐1 Family. Immunol. Rev. 2018, 281, 154–168.
  16. Gautier, V.; Cayrol, C.; Farache, D.; et al. Extracellular IL-33 Cytokine, But Not Endogenous Nuclear IL-33, Regulates Protein Expression in Endothelial Cells. Sci. Rep. 2016, 6, 34255.
  17. Krishnamurthy, H.K.; Reddy, S.; Jayaraman, V.; et al. Association of Micronutrients and Prevalence of Antibodies in Hyperthyroidism. In: Hyperthyroidism—Recent Updates; Gelen, V.; Kükürt, A.; Şengül, E.; Eds.; IntechOpen: London, UK, 2023; pp. 1–15.
  18. Jin, M.; Jang, A.; Kim, C.A.; et al. Long-Term Follow-Up Result of Antithyroid Drug Treatment of Graves' Hyperthyroidism in a Large Cohort. Eur. Thyroid J. 2023, 12.
  19. Phagoora, J.; Bakilwal, S.; Hamzehpour, A.; et al. Graves Disease: A Comprehensive Review. Physician's J. Med. 2024, 3, 1.
  20. Cui, X.; Wang, F.; Liu, C. A Review of TSHR- and IGF-1R-Related Pathogenesis and Treatment of Graves’ Orbitopathy. Front. Immunol. 2023, 14, 1062045.
  21. Rahmah, A.M. Effect of Carbimazole Drug on Some Adipokines and Gene Expression of TSHR at Different Periods in Hyperthyroid Patients. Doctoral dissertation, University of Baghdad, Baghdad, Iraq, July 2021.
  22. Zhou, Z.; Yan, F.; Liu, O. Interleukin (IL)-33: An Orchestrator of Immunity from Host Defense to Tissue Homeostasis. Clin. Transl. Immunol. 2020, 9, e114.
  23. Bao, L.H.; Duc, N.M.; Chien, P.C.; et al. Central Hyperthyroidism Due to Thyroid-Stimulating Hormone-Secreting Pituitary Microadenoma in an Adolescent Boy: Case Report and Review of the Literature. Case Rep. Endocrinol. 2021, 2021, 1–7.
  24. Fariduddin, M.M.; Singh, G. Thyroiditis. In: StatPearls [Internet]; StatPearls Publishing: Treasure Island, FL, USA, 2023.
  25. Qureshi, A.S. Effect of Chronic/High Iodine Intake on Thyroid Function and Fertility. EC Vet. Sci. 2020, 5, 1–9.
  26. Janus, I.; Noszczyk-Nowak, A.; Bubak, J.; et al. Comparative Cardiac Macroscopic and Microscopic Study in Cats with Hyperthyroidism vs. Cats with Hypertrophic Cardiomyopathy. Vet. Q. 2023, 43, 1–11.
  27. Berad, A.; Chaudhari, S.; Chafekar, N. Study of Cardiovascular Manifestations in Patients with Thyroid Dysfunction at Tertiary Care Center. MVP J. Med. Sci. 2020, 7, 246–256.
  28. Bhamare, S.B.; Maru, A.; More, M.Y.; et al. An Overview on Hyperthyroidism. World J. Pharm. Res. 2020, 9, 433–442.
  29. Hussain, F.; Adil, M.; Hussain, M. Radioactive Iodine Therapy for Hyperthyroidism. In: Hyperthyroidism—Recent Updates; IntechOpen: London, UK, 2023.
  30. Kalarani, I.B.; Veerabathiran, R. Impact of Iodine Intake on the Pathogenesis of Autoimmune Thyroid Disease in Children and Adults. Ann. Pediatr. Endocrinol. Metab. 2022, 27, 256–264.
  31. Ayser, I., & Omer, A. (2024). Prostate Cancer Therapy Respones: An ELISA study on the Role of MMP9. Al-Turath Medical Journal, 1(1), 21-29.‏
  32. Ghaemmaghami, Z.; Firoozbakhsh, P.; Gholami, D.; et al. Increased Prevalence of Thyroid Dysfunction in Tehran–HAMRAH Study. BMC Endocr. Disord. 2023, 23, 270.
  33. 4. Aldiri, D. A., Mohammed, I. A., & Al-Obaidi, W. L. (2024). An Investigation into the Levels of Asprosin Hormone and Some Immunological Variables in a Number of Obese Women in the City of Kirkuk. Al-Turath Medical Journal, 1(1), 30-39.‏
  34. Taylor, P.N.; Albrecht, D.; Scholz, A.; et al. Global Epidemiology of Hyperthyroidism and Hypothyroidism. Nat. Rev. Endocrinol. 2018, 14, 301–316.
  35. Zaman, B.; Rasool, S.O.; Sabri, S.M.; et al. Prevalence of Thyroid Dysfunctions in a Large, Unselected Population in Duhok City, Iraqi Kurdistan: A Cross-Sectional Study. J. Biol. Res. Boll. Soc. Ital. Biol. Sperim. 2021, 94, 2.
  36. Tahir, N.T.; Najim, H.D.; Nsaif, A.S. Prevalence of Overt and Subclinical Thyroid Dysfunction Among Iraqi Population in Baghdad City. Iraqi J. Community Med. 2020, 33, 20.
  37. Atia, A. Proceedings of the 5th Libyan Conference on Medical and Pharmaceutical Sciences: Organized by Center of Scientific Research and International Cooperation – University of Tripoli Alahlia. AlQalam J. Med. Appl. Sci. 2021, 4, 1–15.
  38. Rivas, A.M.; Pena, C.; Kopel, J.; et al. Hypertension and Hyperthyroidism: Association and Pathogenesis. Am. J. Med. Sci. 2021, 361, 3–7.
  39. Akber, N.T.; Yenzeel, J.H. Evaluation of Some Biochemical Parameters in Iraqi Patients with Hyperthyroidism. Iraqi J. Biotechnol. 2023, 22, 1.
  40. Mouli, S.; Pradeep, P.; Mishra, A.K. Hyperthyroidism: Surgeon's Perspective. In: Endocrine Surgery; Mishra, A.K., Agarwal, A., Parameswaran, R., Eds.; CRC Press: Boca Raton, FL, USA, 2022; pp. 58–70.
  41. Roa Dueñas, O.H.; Van der Burgh, A.C.; Ittermann, T.; et al. Thyroid Function and the Risk of Prediabetes and Type 2 Diabetes. J. Clin. Endocrinol. Metab. 2022, 107, 1789–1798.
  42. Abdulhadi, M.H.; Al-Kuraishy, H.M.; Al-Gareeb, A.I. Beneficial Effects of Levothyroxine Replacement Therapy on Leptin: Adiponectin Ratio in Patients with Idiopathic Primary Hypothyroidism. J. Pak. Med. Assoc. 2021, 71, s17–s21.
  43. Th, S., Kismat, T., & Ayser, I. (2024). The Role of rs2305948 in Determining Vascular Endothelial Growth Factor Levels in Breast Cancer. Al-Turath Medical Journal, 1(1), 40-48.‏
  44. Fasciolo, G.; Napolitano, G.; Aprile, M.; et al. Hepatic Insulin Resistance in Hyperthyroid Rat Liver: Vitamin E Supplementation Highlights a Possible Role of ROS. Antioxidants 2022, 11, 1295.
  45. Voetterl, H.; van Wingen, G.; Michelini, G.; et al. Brainmarker-I Differentially Predicts Remission to Various Attention-Deficit/Hyperactivity Disorder Treatments: A Discovery, Transfer, and Blinded Validation Study. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 2023, 8, 52–60.
  46. Gunn, A.H.; Frisco, N.; Thomas, S.M.; et al. Patient-Reported Outcomes Following Total Thyroidectomy for Graves’ Disease. Thyroid 2022, 32, 54–64.
  47. Wiersinga, W.M.; Poppe, K.G.; Effraimidis, G. Hyperthyroidism: Aetiology, Pathogenesis, Diagnosis, Management, Complications, and Prognosis. Lancet Diabetes Endocrinol. 2023, 11, 282–297.
  48. Yousif, A.M.; Ataelfadeal, K.A.; Dafalla, A.M.; et al. Serum Lipid Profile Among Sudanese Patients Diagnosed with Hyperthyroidism. Muthanna Med. J. 2022, 9, 2.
  49. Karimi, N.; Neshat, M.; Molazem, M. Comparison of Scintigraphy and CT-Scan Techniques in the Diagnosis of Cat Hyperthyroidism. Vet. Clin. Pathol. Q. Sci. J. 2023, 17, 109–120.
  50. Pooria, A.; Pourya, A.; Gheini, A. Frequency of Pathological Types of Hyperthyroidism in Thyroid Scan Patients. Curr. Med. Imaging 2021, 17, 608–612.
  51. Candellone, A.; Saettone, V.; Badino, P.; et al. Management of Feline Hyperthyroidism and the Need to Prevent Oxidative Stress: What Can We Learn from Human Research? Antioxidants 2021, 10, 1496.
  52. Wang, D.; Zhang, Y.; Shen, C. Research Update on the Association Between SFRP5, an Anti-Inflammatory Adipokine, with Obesity, Type 2 Diabetes Mellitus, and Coronary Heart Disease. J. Clin. Med. 2020, 24, 2730–2735.
  53. Li, D.; Guo, B.; Liang, Q.; et al. Tissue-Engineered Parathyroid Gland and Its Regulatory Secretion of Parathyroid Hormone. J. Tissue Eng. Regen. Med. 2020, 14, 1363–1373.
  54. Sarangi, P.K.; Parida, S.; Mangaraj, S.; et al. Diagnostic Utility of Mean Peak Systolic Velocity of Superior Thyroid Artery in Differentiating Graves’ Disease from Thyroiditis. Indian J. Radiol. Imaging 2021, 31, 311–317.
  55. Jiang, Z.; Huang, L.; Cai, H.; et al. Circular RNA circPHF16 Enhances IL-17A Expression and Secretion by Sequestering miR-378a-3p to Activate the IL6ST Axis in Graves’ Disease. Cytokine 2024, 181, 156681.
  56. Rashied, R.M.; Sameen, A.M.; Shabeeb, I.A. Comparing the Values of Anti-TPO and IL-17 Among Patients with Thyroid Disorders and Comparing Them with Healthy Controls in Ramadi City. City 2022, 6, 2500–2508.
  57. Zaķe, T. Thyroid Autoimmunity: Exploring the Role of Th17-Associated Cytokines and Pathomorphological Mechanisms Involved in the Pathogenesis of Hashimoto’s Thyroiditis and Graves’ Disease. Doctoral Thesis, Riga Stradiņš University, Riga, Latvia, 2021.
  58. Crnčić, T.B.; Girotto, N.; Tomaš, M.I.; et al. Innate Immunity in Autoimmune Thyroid Disease During Pregnancy. Int. J. Mol. Sci. 2023, 24, 15442.
  59. Akhter, S.; Tasnin, F.M.; Islam, M.N.; et al. Role of Th17 and IL-17 Cytokines on Inflammatory and Autoimmune Diseases. Curr. Pharm. Des. 2023, 29, 2078–2090.
  60. Kustrimovic, N.; Gallo, D.; Piantanida, E.; et al. Regulatory T Cells in the Pathogenesis of Graves’ Disease. Int. J. Mol. Sci. 2023, 24, 16432.
  61. Duan, J.; Kang, J.; Deng, T.; et al. Exposure to DBP and High Iodine Aggravates Autoimmune Thyroid Disease Through Increasing the Levels of IL-17 and Thyroid-Binding Globulin in Wistar Rats. Toxicol. Sci. 2018, 163, 196–205.
  62. Tywanek, E.; Michalak, A.; Świrska, J.; et al. Autoimmunity, New Potential Biomarkers, and the Thyroid Gland—The Perspective of Hashimoto’s Thyroiditis and Its Treatment. Int. J. Mol. Sci. 2024, 25, 4703.
  63. Shakerian, L.; Kolahdooz, H.; Garousi, M.; et al. IL-33/ST2 Axis in Autoimmune Disease. Cytokine 2022, 158, 156015.
  64. Qiu, H.; Ni, C.; Jia, C.; et al. CircRNA7632 Down-Regulation Alleviates Endothelial Cell Dysfunction in Kawasaki Disease via Regulating IL-33 Expression. Cell Stress Chaperones 2023, 28, 363–374.
  65. Cayrol, C. IL-33, an Alarmin of the IL-1 Family Involved in Allergic and Nonallergic Inflammation: Focus on the Mechanisms of Regulation of Its Activity. Cells 2021, 11, 107.