Биология ва тиббиёт муаммолари 2025 №5 (165)
Тема статьи
THE ROLE OF INTERLEUKIN-6 IN THE PATHOPHYSIOLOGY, PROGNOSIS, AND THERAPEUTIC TARGETING OF HEART FAILURE WITH REDUCED EJECTION FRACTION (375-378)
Авторы
Samieva Gulnoza Utkurovna, Rakhmonov Sardor Temurkul ugli
Учреждение
Samarkand State Medical University, Republic of Uzbekistan, Samarkand
Аннотация
Heart failure with reduced ejection fraction (HFrEF) remains one of the leading causes of morbidity and mortality worldwide, and inflammation has emerged as a major non-hemodynamic driver of its progression. Among inflammatory mediators, interleukin-6 (IL-6) plays a particularly central role in linking systemic inflammation, myocardial remodeling, and adverse outcomes. This review discusses current evidence on the pathophysiological and prognostic significance of IL-6 in HFrEF and explores its potential as a therapeutic target. Elevated IL-6 activates the JAK/STAT3 and MAPK signaling pathways, promoting myocardial fibrosis, hypertrophy, and apoptosis, and contributes to endothelial dysfunction and metabolic disturbance. Population-based studies, such as the MESA cohort, demonstrate that increased IL-6 levels precede heart failure onset, while Mendelian randomization analyses confirm a causal relationship between IL6R variants and cardiometabolic risk. Clinically, IL-6 correlates with disease severity and hospitalization, outperform-ing other cytokines such as TNF-α as a chronic biomarker. Recent trials, including HERMES, suggest that IL-6 inhibition with ziltivekimab can reduce systemic inflammation and cardiac stress, although definitive evidence in HFrEF is still lacking. Standard therapies like SGLT2 inhibitors and ARNIs may also exert secondary IL-6–lowering effects. Taken together, IL-6 represents both a pathogenic mediator and a promising target in HFrEF. Future research must clarify whether selective IL-6 blockade can translate into improved survival and reverse remodeling, marking a transition toward an era of precision anti-inflammatory cardiology.
Ключевые слова
Interleukin-6, heart failure, inflammation, fibrosis, JAK/STAT3, ziltivekimab, HFrEF.
Литературы
1. Alimjanovich R. Z. et al. Dental condition after bariatric operations // Journal of Modern Educational Achievements. – 2023. – Т. 9. – №. 9. – С. 206-215. 2. Adilov K. Z., Rizaev J. A., Adilova Sh T. Diagnostic and prognostic significance of gingival fluid cytokines in the development of inflammatory periodontal diseases // The American Journal of Medical Sciences and Pharmaceutical Research. – 2024. – Т. 6. – №. 07. – С. 12-18. 3. Boulet J, Sridhar VS, Bouabdallaoui N, Tardif JC, White M. Inflammation in heart failure: Pathophysiology and therapeutic strategies. Inflamm Res. 2024;73(5):709-723. 4. Albar Z, Albakri M, Hajjari J, Karnib M, Janus SE, Al-Kindi SG. Inflammatory markers and risk of heart failure with reduced to preserved ejection fraction. Am J Cardiol. 2022;167:68-75. 5. Alogna A, Koepp KE, Sabbah M, Espindola Netto JM, Jensen MD, Kirkland JL, et al. Interleukin-6 in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2023;11(11):1549-1561. 6. Boulet J, Sridhar VS, Bouabdallaoui N, Tardif JC, White M. Inflammation in heart failure: Pathophysiology and therapeutic strategies. Inflamm Res. 2024;73(5):709-723. 7. Ahmed SA, Ismail HM, Alahmedi AB, Alahmadi FB, Muhawish AF, Alsubhi AA, et al. Decoding the inflammatory pathway in heart failure: The role of interleukins and tumor necrosis factor-alpha in disease severity. J Clin Med. 2025;14(17):6092. 8. Chia YC, Kieneker LM, Van Hassel G, Binnenmars SH, Nolte IM, Van Zanden JJ, et al. Interleukin-6 and development of heart failure with preserved ejection fraction in the general population. J Am Heart Assoc. 2021;10(11):e018549. 9. Cupido AJ, Asselbergs FW, Natarajan P, Ridker PM, Hovingh GK, Schmidt AF. Dissecting the IL-6 pathway in cardiometabolic disease: A Mendelian randomization study on both IL6 and IL6R. Br J Clin Pharmacol. 2022;88(6):2875-2884. 10. Gui XY, Rabkin SW. C-reactive protein, interleukin-6, trimethylamine-N-oxide, syndecan-1, nitric oxide, and tumor necrosis factor receptor-1 in heart failure with preserved versus reduced ejection fraction: A meta-analysis. Curr Heart Fail Rep. 2023;20(1):1-11. 11. Katkenov N, Mukhatayev Z, Kozhakhmetov S, Sailybayeva A, Bekbossynova M, Kushugulova A. Systematic review on the role of IL-6 and IL-1β in cardiovascular diseases. J Cardiovasc Dev Dis. 2024;11(7):206. 12. Povar-Echeverría M, Auquilla-Clavijo PE, Andrès E, Martin-Sánchez FJ, Laguna-Calle MV, Calvo-Elías AE, et al. Interleukin-6 could be a potential prognostic factor in ambulatory elderly patients with stable heart failure. J Clin Med. 2021;10(3):504. 13. Rizaev J. A., Vohidov E. R., Nazarova N. S. The importance of the clinical picture and development of the condition of periodont tissue diseases in pregnant women // Central Asian Journal of Medicine. – 2024. – №. 2. – С. 85-90. 14. Rizaev J. A. et al. Analysis of active mechanisms for modulating the blood flow of the microvasculature in patients with periodontitis on the background of coronary heart disease complicated by chronic heart failure // Вісник проблем біології і медицини. – 2019. – Т. 1. – №. 4. – С. 338-342. 15. Rizaev E. A. et al. Optimization of guided bone regeneration in conditions of jaw bone atrophy // Applied Information Aspects of Medicine (Prikladnye informacionnye aspekty mediciny). – 2022. – Т. 25. – №. 4. – С. 4-8. 16. Takagi K, Barros M, Davison BA, Cotter G. Inflammation and corticosteroids in acute heart failure. Eur J Emerg Med. 2023;30(2):65-66. 17. Vasques-Nóvoa F, Ferreira JP, Marques P, Neves JS, Vale C, Ribeirinho-Soares P, et al. Interleukin-6, infection and cardiovascular outcomes in acute heart failure: Findings from the EDIFICA registry. Cytokine. 2022;160:156053. 18. Wang C, Qin Y, Zhang X, Yang Y, Wu X, Liu J, et al. Effect of dapagliflozin on indicators of myocardial fibrosis and levels of inflammatory factors in heart failure patients. Dis Markers. 2022;2022:5834218. 19. Xie L, Li S, Yu X, Wei Q, Yu F, Tong J. DAHOS study: Efficacy of dapagliflozin in treating heart failure with reduced ejection fraction and obstructive sleep apnea syndrome. Eur J Clin Pharmacol. 2024;80(5):771-780.