PERBANDINGAN EKSPRESI IL-4 PADA PASIEN PENYAKIT JANTUNG REMATIK DENGAN BERBAGAI DERAJAT KALSIFIKASI KATUP MITRAL
Keywords:
IL-4, Rheumatic Heart Disease (RHD), mitral valve calcificationAbstract
Background: Rheumatic heart disease (RHD) remains a major cause of heart valve disease in developing countries, with mitral valve calcification being a common manifestation. Inflammatory and anti-inflammatory cytokines are involved in the pathogenesis of valvular damage. Interleukin-4 (IL-4), an anti- inflammatory cytokine, has been reported to modulate inflammatory responses and inhibit calcification through several biological mechanisms; however, its role at the tissue level in rheumatic mitral valve calcification is not yet fully understood.
Objectives: This study aimed to compare IL-4 expression in patients with RHD across different degrees of mitral valve calcification.
Methods: This observational cross-sectional study included 19 patients diagnosed with RHD who underwent mitral valve replacement surgery at Sardjito Hospital. Mitral valve tissues were collected for histopathological and immunohistochemical examination. IL-4 expression was evaluated semi- quantitatively using immunohistochemical staining and categorized as low or high expression. The degree of mitral valve calcification was determined based on echocardiographic findings. Differences in IL-4 expression among various calcification grades were analyzed using the Mann–Whitney test.
Results: Among the 19 patients, 63.2% were female and 89.5% were older than 30 years. All patients exhibited mitral valve calcification, predominantly grades 2 and 3. Statistical analysis showed no significant differences in IL-4 expression across different degrees of mitral valve calcification (p > 0.05).
Conclusion: IL-4 expression did not differ significantly among patients with varying degrees of mitral valve calcification in RHD. These findings suggest that IL-4 alone may not determine calcification severity and support the multifactorial nature of valvular calcification in rheumatic heart disease. Further studies involving co-existing cytokines are warranted to better elucidate the underlying immunopathogenesis.
References
1. Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019. Journal of the American College of Cardiology. 2020 Dec;76(25):2982–3021.
2. Watkins DA, Johnson CO, Colquhoun SM, Karthikeyan G, Beaton A, Bukhman G, et al. Global, Regional, and National Burden of Rheumatic Heart Disease, 1990–2015. N Engl J Med. 2017 Aug 24;377(8):713–22.
3. Krohn JB, Hutcheson JD, Martínez-Martínez E, Aikawa E. Extracellular vesicles in cardiovascular calcification: expanding current paradigms. The Journal of Physiology. 2016 June;594(11):2895–903.
4. Passos LSA, Nunes MCP, Aikawa E. Rheumatic Heart Valve Disease Pathophysiology and Underlying Mechanisms. Front Cardiovasc Med. 2021 Jan 18;7:612716.
5. Dong C, Fu T, Ji J, Li Z, Gu Z. The role of interleukin-4 in rheumatic diseases. Clin Exp Pharma Physio. 2018 Aug;45(8):747–54.
This is an open access article under CC-BY-SA license (https://creativecommons.org/licenses/by-sa/4.0/ )|41 - 42
Berkala Kesehatan Klinik, Vol. 19, No. 1, 2025: 33-42
6. Celik MÖ, Labuz D, Keye J, Glauben R, Machelska H. IL-4 induces M2 macrophages to produce sustained analgesia via opioids. JCI Insight. 2020 Feb 27;5(4):e133093.
7. Atri C, Guerfali FZ, Laouini D. Role of Human Macrophage Polarization in Inflammation during Infectious Diseases. IJMS. 2018 June 19;19(6):1801.
8. Ralph AP, Currie BJ. Therapeutics for rheumatic fever and rheumatic heart disease. Aust Prescr. 2022 Aug 1;45(4):104–12.
9. Brown MA, Hural J. Functions of IL-4 and Control of Its Expression. Crit Rev Immunol. 2017;37(2–6):181–212.
10. Guilherme L, Köhler K, Postol E, Kalil J. Genes, autoimmunity and pathogenesis of rheumatic heart disease. Ann Pediatr Card. 2011;4(1):13.
11. TekerE,Akadam-TekerAB,OzturkO,EronatAP,YalinK,GolcukSE,etal.Association Between the Interferon Gamma 874 T/A Polymorphism and the Severity of Valvular Damage in Patients with Rheumatic Heart Disease. Biochem Genet. 2018 June;56(3):225–34.
12. Yusuf J, P J, Mukhopadhyay S, Vignesh V, Tyagi S. Evaluation of serum 25- hydroxyvitamin D levels in calcific rheumatic mitral stenosis— A cross sectional study. Indian Heart Journal. 2018 Mar;70(2):206–13.
13. Xie T, Chen X, Liu C, Cai X, Xiang M, Liu S, et al. New insight into the role of lipid metabolism-related proteins in rheumatic heart valve disease. Lipids Health Dis. 2022 Oct 28;21(1):110.
