Pyvovar S. M., Rudyk Yu. S., Lozyk T. V., Krotova O. B., Galchinska V. Yu., Chenchik T. O.

ASSOCIATION OF CLINICAL COURSE OF HEART FAILURE WITH INTERLEUKIN LEVELS IN PATIENTS WITH NONTOXIC GOITER


About the author:

Pyvovar S. M., Rudyk Yu. S., Lozyk T. V., Krotova O. B., Galchinska V. Yu., Chenchik T. O.

Heading:

CLINICAL AND EXPERIMENTAL MEDICINE

Type of article:

Scentific article

Annotation:

Heart failure (HF), as the final stage of the cardiovascular continuum, is associated with high mortality in most countries of the world. It is known that concomitant diseases and dynamics of a number of hormones, biomarkers, including interleukins (IL), are associated with the course of HF. Some ILs have predictive value that exceeds the accuracy of traditional risk markers. Non-toxic goiter (NTG) is one of the most common thyroid pathologies in our country. ILs play a role in the development of thyroid pathology. We know about the correlation with cytokines and serum levels of thyroid hormones. A study by scientists from Poland showed that human thyrocytes can synthesize ILs that activate T and B lymphocytes. The authors demonstrated that in patients with NTG there is an increase in the concentration of proinflammatory IL. It is possible to assume that there are certain features of the influence of IL on the course of HF in patients with NTG. Objective: to study the relationship of the clinical course of heart failure (HF) in patients with non-toxic goiter (NTG) with blood levels of interleukins (IL). Object and research methods. 354 patients with heart failure on the background of post-infarction cardiosclerosis were included. In 205 (57.9 %) patients, NS was diagnosed. The levels of tumor necrosis factor-a (TNFa), IL-1β, IL-4, IL-6, TSH, T3f and T4f were determined. Echocardioscopy and ultrasound of the thyroid gland (TG) were performed. The course of HF for 2 years was studied. Results. Compared with the data in the reference group, patients with heart failure have higher levels of TNFa (by 38.8 %, p <0.0001), IL-6 (by 116.4 %, p <0.0001) and low the concentration of IL 4 (by 27.3 %, p <0.0001), as well as a larger value of the ratio of IL-1β/IL-4 (by 37.9 %, p <0.0001). Patients with heart failure in combination with low triiodothyronine syndrome (LTS) and NTG have significantly lower levels of IL-1β (by 21.9 %, p = 0.03) and IL-4 (by 11.5 %, p = 0.04). Patients without NTG who died within two years of observation had a higher level of TNFα (by 29.2 %, p = 0.01), and patients with a combined endpoint (CEP) tended to increase the content of IL-1β (by 16.6 %, p = 0.05). In patients with heart failure and with NG who had re-hospitalization, the level of IL-4 was significantly lower (by 14.4 %, p = 0.04), compared with that in patients with a favorable course of heart failure. A similar pattern was found in patients who had CEP (by 14.4 %, p = 0.02). Conclusions. Interleukin levels may be associated with HF in patients with NTG. Patients with the above pathologies in combination with TNF have significantly lower levels of IL-1β and IL-4. In patients with HF in combination with NTG with re-hospitalization or CEP, the level of IL-4 is significantly lower. Patients without NTG who died had a higher level of TNFa, and patients with CEP tended to increase the content of IL-1β.

Tags:

heart failure, non-toxic goiter, low T3 syndrome, tumor necrosis factor, interleukins, the course of the disease.

Bibliography:

  1. Voronkov LH, Amosova KM, Bahriy AE, Dziak GV, Diadik OI, Zarinov OI, ta in. Rekomendatsiyi Asotsiatsiyi kardiolohiv Ukrayiny z diahnostyky, likuvannya ta profilaktyky khronichnoyi sertsevoyi nedostatnosti u doroslykh. Kyyiv; 2009. s. 4-22. [in Ukrainian].
  2. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2016. The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal. 2016;8:2129-200. DOI: 10.1093/eurheartj/ehw128
  3. Aukrust P, Ueland T, Lien E, Bendtzen K, Muller F, Andreassen AK, et al. Cytokine network in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 1999;83:376-82.
  4. Deswal A, Petersen NJ, Feldman AM, Young JB, White BG, Mann DL. Cytokines and cytokine receptors in advanced heart failure. Circulation. 2001;103:2055-9. DOI: 10.1161/01.cir.103.16.2055
  5. Yuzvenko TYu. Osoblyvosti perebihu tsukrovoho diabetu 2-ho typu u poyednanni z hipotyreozom. Mizhnarodnyy endokrynolohichnyy zhurnal. 2015;8(72):73-7. DOI: 10.22141/2224-0721.8.72.2015.72341 [in Ukrainian].
  6. Provatopoulou X, Georgiadou D, Sergentanis TN, Kalogera E, Spyridakis J, Gounaris A, et al. Interleukins as markers of inflammation in malignant and benign thyroid disease. Inflammation Research. 2014;63:667-74. DOI: 10.1007/s00011-014-0739-z
  7. Abo-Zenah HA, Shoeb SA, Sabry AA, Ismail HA. Relating circulating thyroid hormone concentrations to serum interleukins-6 and -10 in association with non-thyroidal illnesses including chronic renal insufficiency. BMC Endocrine Disorders. 2008 Jan 22;8:1. DOI: 10.1186/1472- 6823-8-1
  8. Bossowski A, Urban M. Serum levels of cytokines in children and adolescents with Graves' disease and non-toxic nodular goiter. J Pediatr Endocrinol Metab. 2001;14(6):741-7.
  9. Pyvovar SM, Rudyk YuS, Lozyk TV, Galchinska VYu, Chenchik TO. Osoblyvosti vyznachennya syndromu «nyz’koho tryyodtyroninu» pry sertseviy nedostatnosti ta yoho vplyv na perebih zakhvoryuvannya. Zaporizʹkyy medychnyy zhurnal. 2019;4(21):437-43. [in Ukrainian].
  10.  Bekkering GE, Agoritsas T, Lytvyn L, Heen AF, Feller M, Moutzouri E, et al. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019;365. DOI: https://doi.org/10.1136/bmj.l2006 (Published 14 May 2019).
  11.  Belovol AN, Knyaz'kova II. Antagonisty mineralo-kortikoidnykh retseptorov pri serdechnoy nedostatochnosti: chto my o nikh znayem i kak dolzhny ispol'zovat'. Sertseva nedostatníst' ta komorbídní stani. 2017;1:15-29. [in Russiаn].
  12. Berezin AYe. Vyzhivaniye patsiyentov s serdechnoy nedostatochnost'yu so snizhennoy fraktsiyey vybrosa i ishemicheskoy bolezn'yu serdtsa pri primenenii invazivnykh i konservativnykh strategiy lecheniya: rezul'taty metaanaliza. Sertseva nedostatníst' ta komorbídní stani. 2017;3:12- 26. [in Russiаn].
  13. Tan GH, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med. 1997 Feb 1;126(3):226-31.
  14. Grubeck-Loebenstein B, Buchan G, Chantry D, Kassal H, Londei M, Pirich K, et al. Analysis of intrathyroidal cytokine production in thyroid autoimmune disease: thyroid follicular cells produce interleukin-loc and interleukin-6. Clin. Exp. Immunol. 1989;77:324-30.
  15. Bujak M. The role of IL-1 in the pathogenesis of heart disease. Arch. Immunol. Ther. Exp. 2009;57(3):165-76.
  16. Bozkurt B, Kribbs SB, Clubb FJ, Michael LH, Didenko VV, Hornsby PJ, et al. Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive dysfunction and remodelling in rats. Circulation. 1998;97:1382-91.
  17. Fischer P, Hilfiker-Kleiner D. Role of gp130-mediated signalling pathways in the heart and its impact on potential therapeutic aspects. Br J Pharmacol. 2008;153(1):414-27.
  18. Mann DL. Inflammatory mediators and the failing heart: past, present, and the foreseeable future. Circ Res. 2002;91:988-98.
  19. Kosmala W. Plasma levels of TNF-alpha, IL-6, and IL-10 and their relationship with left ventricular diastolic function in patients with stable angina pectoris and preserved left ventricular systolic performance. Coron. Artery Dis. 2008;19(6):375-82. DOI: 10.1097/MCA.0b013e3282fc617c
  20. Hedayat M, Mahmoudi MJ, Rose NR. Proinflammatory cytokines in heart failure: double-edged swords. Heart Fail Rev. 2010;15(6):543-62. DOI: 10.1007/s10741-010-9168-4
  21. Mebis L, Van den Berghe G. Thyroid axis function and dysfunction in critical illness. Best Pract Res Clin Endocrinol Metab. 2011 Oct;25(5):745- 57. DOI: 10.1016/j.beem.2011.03.002
  22.  Moura Neto A, Parisi MC, Alegre SM, Pavin EJ, Tambascia MA, Zantut-Wittmann DE. Relation of thyroid hormone abnormalities with subclinical inflammatory activity in patients with type 1 and type 2 diabetes mellitus. Endocrine. 2016 Jan;51(1):63-71. DOI: 10.1007/s12020-015-0651-5
  23. Opasich C, Pacini F, Ambrosino N. Sick euthyroid syndrome in patients with moderate-to-severe chronic heart failure. European Heart Journal. 1996;17(12):1860-6.
  24. Manowitz NR, Mayor GH, Klepper MJ, DeGroot LJ. Subclinical hypothyroidism and euthyroid sick syndrome in patients with moderate-tosevere congestive heart failure. American Journal of Therapeutics. 1996;3(12):797-801.
  25.  Iervasi G, Pingitore A, Landi P. Low-T3 syndrome: a strong prognostic predictor of death in patients with heart disease. Circulation. 2003;107(5):708-13.
  26. Testa M, Yeh M, Lee P, Fanelli R, Loperfido F, Berman JW, et al. Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension. J Am Coll Cardiol. 1996;28:964-71.
  27. Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, Mann DL. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol. 1996;27:1201-6.
  28. Aukrust P, Ueland T, Muller F, Andreassen AK, Aass H, Kjekshus J, et al. Elevated circulating levels of C-C chemokines in patients with congestive heart failure. Circulation. 1998;97:1136-43.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 1 (155), 2020 year, 187-193 pages, index UDK 616.12-008.46-085.22:616.441-006.5]-092:575.174.015.3:612.017

DOI: