Сytokines as non-hormonal regulators in the pathogenesis of endocrinopathies
- 作者: Valikova O.V.1,2,3, Zdor V.V.1,3, Sarychev V.A.1,4, Tikhonov Y.N.1, Boroda A.V.5
-
隶属关系:
- Pacific State Medical University
- Regional Clinical Hospital No. 2, Vladivostok
- Cliniсs for Diabetes and Endocrine Diseases, Vladivostok
- Clinical Hospital “RZhD-Medicine”
- A. Zhirmunsky National Scientific Center of Marine Biology, Far East Branch, Russian Academy of Sciences
- 期: 卷 26, 编号 4 (2023)
- 页面: 507-514
- 栏目: Forum Sochi 2023
- URL: https://journals.rcsi.science/1028-7221/article/view/253434
- DOI: https://doi.org/10.46235/1028-7221-13959-CAN
- ID: 253434
如何引用文章
全文:
详细
Cytokines regulate the activity of hypothalamus – pituitary – adrenal hormonal axis, also affecting thyroid gland and ovaries. However, their exact role in pathogenesis of endocrine diseases is still under study. Altered cytokine secretion in autoimmune thyroid diseases and polycystic ovary syndrome is well known. Meanwhile, the main immunological predictors of severe prognosis in endocrinopathies and biomarkers for administration of targeted immunotherapy have not yet been determined. Therefore, our objective was to study the relationships between the cytokines and hormones in pathogenesis of autoimmune and non-autoimmune endocrinopathies, i.e., autoimmune thyroiditis (AIT), Graves’ disease (GD), nodular and multinodular goiter, polycystic ovary syndrome (PCOS).
101 patients with GD and 105 patients with AIT, 110 patients with PCOS were examined; 51 patients with nodular and multinodular euthyroid goiter and 50 healthy individuals; their average age was 34.5±2.9 years old. The study was approved by the Interdisciplinary Ethics Committee of the Pacific State Medical University. Clinical examination included ultrasonography. ELISA technique was applied for determination of thyroid and sex hormones, TSH, autoantibodies to TPO, TSH receptor, cytokines in blood serum, in follicular fluid samples, cell culture media (primary cultures of cumulus cells). Genetic studies were carried out with PCR. Morphological verification was performed by inverted microscopy CKX41 (Olympus) with a phase contrast system, camera AxioCam5 (Carl Zeiss) with software Zen 2, Blue Edition.
IL-6 and TNFα in the blood serum of patients with PCOS were most significantly increased, Sharply decreased IFNγ/IL-10 ratio in blood serum and cumulus cell culture was found in PCOS when compared with controls. Significant changes in the content of thyroid hormones in GD and TSH in AIT have been proven to affect the hyperproduction of pro- and anti-inflammatory cytokines. Before treatrment, the direct or reverse corelations were found between the levels of cytokines and thyroid hormones in GD, and TSH in AIT. Subsequently, upon correction of hormonal disorders, these associations became weaker, or faded away. In patients with nodular and multinodular euthyroid goiter, only the IFNγ level was significantly increased, being twice as high as in the control group.
A significant imbalance in the ratio of Th1/Th2 marker cytokines and their hyperproduction in autoimmune thyroid diseases made it possible to characterize the cellular response system in autoimmune thyroid disorders as highly active and directly associated with thyroid dysfunction, performing its effector function under the impaired immunoregulation. The revealed changes in pro-inflammatory cytokines in polycystic ovary syndrome represent new immunological markers of fertility, which may be a promising target for pathogenetic immunotherapy.
作者简介
Olga Valikova
Pacific State Medical University; Regional Clinical Hospital No. 2, Vladivostok; Cliniсs for Diabetes and Endocrine Diseases, Vladivostok
Email: renalex.99@mail.ru
Junior Research Associate, Pacific State Medical University; Clinical Endocrinologist, Regional Clinical Hospital No. 2; Clinical Endocrinologist, Cliniсs for Diabetes and Endocrine Diseases
俄罗斯联邦, Vladivostok; Vladivostok; VladivostokV. Zdor
Pacific State Medical University; Cliniсs for Diabetes and Endocrine Diseases, Vladivostok
Email: renalex.99@mail.ru
PhD, MD (Medicine), Leading Research Associate, Central Research Laboratory, Pacific State Medical University; Clinical Endocrinologist, Cliniсs for Diabetes and Endocrine Diseases
俄罗斯联邦, Vladivostok; VladivostokV. Sarychev
Pacific State Medical University; Clinical Hospital “RZhD-Medicine”
编辑信件的主要联系方式.
Email: renalex.99@mail.ru
Postgraduate Student, Department of Normal and Pathological Physiology, Pacific State Medical University; Surgeon, Clinical Hospital “RZhD-Medicine”
俄罗斯联邦, Vladivostok; VladivostokYa. Tikhonov
Pacific State Medical University
Email: renalex.99@mail.ru
Senior Lecturer, Department of Pathological Anatomy, Pacific State Medical University
俄罗斯联邦, VladivostokAndrey Boroda
A. Zhirmunsky National Scientific Center of Marine Biology, Far East Branch, Russian Academy of Sciences
Email: renalex.99@mail.ru
PhD (Biology), Senior Research Associate, Deputy Director for Research, A. Zhirmunsky National Scientific Center of Marine Biology, Far East Branch, Russian Academy of Sciences
俄罗斯联邦, Vladivostok参考
- Antunes T.T., Gagnon A., Bell A., Sorisky A. Thyroid-stimulating hormone stimulates interleukin-6 release from 3T3-L1 adipocytes through a cAMP-protein kinase A pathway. Obes. Res., 2005, Vol. 13, no. 12, pp. 2066-2071.
- Chen L., Zhang Z., Huang J., Jin M. Association between rs1800795 polymorphism in the interleukin-6 gene and the risk of polycystic ovary syndrome: A meta-analysis. Medicine (Baltimore), 2018, Vol. 97, no. 29, e11558. doi: 10.1097/MD.0000000000011558.
- de Alencar J.B., Alves H.V., Elpidio L.N., Visentainer J.E., Sell A.M. Polymorphisms of cytokine genes and polycystic ovary syndrome: a review. Metab. Syndr. Relat. Disord., 2016, Vol. 14, no. 10, pp. 468-474.
- Escobar-Morreale H.F., Carmina E., Dewailly D., Gambineri A., Kelestimur F., Moghetti P., Pugeat M., Qiao J., Wijeyaratne C.N., Witchel S.F., Norman R.J. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the androgen excess and polycystic ovary syndrome society. Hum. Reprod. Update, 2012, Vol. 18, no. 2, pp. 146-170.
- Jiang D., Ma S., Jing F., Xu C., Yan F., Wang A., Zhao J. Thyroid-stimulating hormone inhibits adipose triglyceride lipase in 3T3-L1 adipocytes through the PKA pathway. PLoS One, 2015, Vol. 10, no. 1, e0116439. doi: 10.1371/journal.pone.0116439.
- Ma S., Jing F., Xu C., Zhou L., Song Y., Yu C., Jiang D., Gao L., Li Y., Guan Q., Zhao J. Thyrotropin and obesity: increased adipose triglyceride content through glycerol-3-phosphate acyltransferase 3. Sci. Rep., 2015, Vol. 5, 7633. doi: 10.1038/srep07633.
- Maiorino M.I., Bellastella G., Giugliano D., Esposito K. From inflammation to sexual dysfunctions: a journey through diabetes, obesity, and metabolic syndrome. J. Endocrinol. Invest., 2018, Vol. 41, no. 11, pp. 1249-1258.
- Mariotti S., Beck-Peccoz P. Physiology of the hypothalamic-pituitary-thyroid axis. 2021 Apr 20. In: Feingold K.R., Anawalt B., Blackman M.R., Boyce A., Chrousos G., Corpas E., de Herder W.W., Dhatariya K., Dungan K., Hofland J., Kalra S., Kaltsas G., Kapoor N., Koch C., Kopp P., Korbonits M., Kovacs C.S., Kuohung W., Laferrère B., Levy M., McGee E.A., McLachlan R., New M., Purnell J., Sahay R., Shah A.S., Singer F., Sperling M.A., Stratakis C.A., Trence D.L., Wilson D.P., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. ID: NBK278958.
- Mueller S., Kleinau G., Szkudlinski M.W., Jaeschke H., Krause G., Paschke R. The superagonistic activity of bovine thyroid-stimulating hormone (TSH) and the human TR1401 TSH analog is determined by specific amino acids in the hinge region of the human TSH receptor. J. Biol. Chem., 2009, Vol. 284, no. 24, pp. 16317-16324.
- Rudnicka E., Suchta K., Grymowicz M., Calik-Ksepka A., Smolarczyk K., Duszewska A.M., Smolarczyk R., Meczekalski B. Chronic low grade inflammation in pathogenesis of PCOS. Int. J. Mol. Sci., 2021, Vol. 22, no. 7, 3789. doi: 10.3390/ijms22073789.
- Siemińska L., Wojciechowska C., Walczak K., Borowski A., Marek B., Nowak M., Kajdaniuk D., Foltyn W., Kos-Kudła B. Associations between metabolic syndrome, serum thyrotropin, and thyroid antibodies status in postmenopausal women, and the role of interleukin-6. Endokrynol. Pol., 2015, Vol. 66, no. 5, pp. 394-403.
- Walczak K., Sieminska L. Obesity and thyroid axis. Int. J. Environ. Res. Public Health, 2021, Vol. 18, no. 18, 9434. doi: 10.3390/ijerph18189434.
- Wang D., Weng Y., Zhang Y., Wang R., Wang T., Zhou J., Shen S., Wang H., Wang Y. Exposure to hyperandrogen drives ovarian dysfunction and fibrosis by activating the NLRP3 inflammasome in mice. Sci. Total Environ., 2020, Vol. 745, 141049. doi: 10.1016/j.scitotenv.2020.141049.
- Yang C., He Z., Zhang Q., Lu M., Zhao J., Chen W., Gao L. TSH activates macrophage inflammation by G13- and G15-dependent Pathways. Endocrinology, 2021, Vol. 162, no. 8, bqab077. doi: 10.1210/endocr/bqab077.
- Zdor V.V., Geltser B.I., Eliseikina M.G., Markelova E.V., Tikhonov Y.N., Plekhova N.G., Karaulov A.V. Roles of thyroid hormones, mast cells, and inflammatory mediators in the initiation and progression of autoimmune thyroid diseases. Int. Arch. Allergy Immunol., 2020, Vol. 181, no. 9, pp. 715-726.
补充文件
