Association of level of IL-6, IL-10, IL-18, tumour necrosis factor-α with rheumatic mitral stenosis and subsequent pulmonary hypertension
DOI:
https://doi.org/10.18203/2349-3933.ijam20220027Keywords:
Rheumatic mitral stenosis, Interleukins, Pulmonary hypertensionAbstract
Background: Objective of the study was to provide insight on the immune response in patients of rheumatic heart disease, mitral stenosis and evaluation of various cytokines in pulmonary hypertension secondary to rheumatic heart disease.
Methods: Total 163 subjects, more than 18 year of age, were enrolled in this study. 84 subjects with rheumatic mitral stenosis (group A) diagnosed on two-dimensional echocardiography (2D echo) and 79 normal healthy volunteers (group B). Patients with mitral stenosis were further divided into subgroups based on severity of mitral stenosis [mitral valve area (MVA >1 cm2 and MVA <1 cm2) (subgroup Aa and Ab)] and presence or absence of pulmonary hypertension [pulmonary arterial systolic pressure (PASP >36 mm Hg) (subgroup Ac and Ad)]. Interleukins IL-6, IL-10, IL-18, tumour necrosis factor alpha (TNF-α) and high-sensitivity C-reactive protein (hs-CRP) levels were assessed in both groups.
Results: Mean IL-6, IL-10, IL-18, TNF-α and hs-CRP in group A and group B was 6.57±3.53 and 2.73±1 (p≤0.001), 8.185±2.8 and 3.51±0.86 (p≤0.001), 136.31±89.0 and 47.96±9.76 (p≤0.001), 21.26±18.59 and 5.36±3.57 (p≤0.001), 4.69±6.3 and 2.63±2.22 (p≤0.008) respectively. On subgroup analysis mean TNF-α in subgroup Aa was 20.71±16.84, while in subgroup Ab was 7.56±1.93 (p≤0.001). Mean IL-10 in subgroup Ac and Ad was 8.74±3.29 and 7.47±1.82, respectively. Differences in levels of other cytokines in these subgroups were not found statistically significant.
Conclusions: This study finds increased IL-6, IL-10, IL-18, TNF-α and hs-CRP levels in subjects with rheumatic mitral stenosis. Subjects with severe mitral stenosis had increased TNF-α levels. Subjects of mitral stenosis having pulmonary hypertension had increased IL-10 levels.
References
Rheumatic fever and rheumatic heart disease: report of a WHO expert consultation, Geneva. World Health Organ Tech Rep Ser. 2004;923:1-122.
Carapetis JR. Rheumatic heart disease in developing countries. N Engl J Med. 2007;357(5):439-41.
Chopra P, Gulwani H. Pathology and pathogenesis of rheumatic heart disease. Indian J Pathol Microbiol. 2007;50(4):685-97.
Guilherme L, Kalil J. Rheumatic fever and rheumatic heart disease: cellular mechanisms leading autoimmune reactivity and disease. J Clin Immunol. 2010;30(1):17-23.
Guilherme L, Köhler KF, Postol E, Kalil J. Genes. Autoimmunity and pathogenesis of rheumatic heart disease. Ann Pediatr Cardiol. 2011;4(1):13-21.
Sedgwick JD, Rininton DS, Cyster JG, Komer H. Tumor necrosis factor: a master regulator of leukocyte movement. Immunol Today. 2000;21:110-3.
Sharma N, Toor D. Interleukin-10: Role in increasing susceptibility and pathogenesis of rheumatic fever/rheumatic heart disease. Cytokine. 2017;90:169-76.
Rudsky LG, Lai WW, Afilalo J. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685-713.
Toor D, Vohra H. Immune responsiveness during disease progression from acute rheumatic fever to chronic rheumatic heart disease. Microbes Infect. 2012;14(12):1111-7.
Serag AR, Hazaa SM, Afifi IK, Ghoname NF. Regulated upon activation, normal T-cell expressed and secreted chemokine and interleukin-6 in rheumatic pulmonary hypertension, targets for therapeutic decision. Eur J of Cardio-thoracic Surgery. 2010;37:853-8.
Rahim SS, Khan N, Boddupalli CS, Hasnain SE, Mukhopadhyay S. Interleukin-10 (IL-10) mediated suppression of IL-12 production in RAW 264.7 cells also involves c-rel transcription factor. Immunology. 2005;114(3):313-21.
Leão SC, Lima MR, Nascimento HM, Octacilio-Silva S, Rodrigues TM. IL-10 and ET-1 as biomarkers of rheumatic valve disease. Rev Bras Cir Cardiovasc. 2014;29(1):25-30.
Guilherme L, Cury P, Demarchi LM, Coelho V, Abel L, Lopez AP, Oshiro SE, Aliotti S, Cunha-Neto E, Pomerantzeff PM, Tanaka AC, Kalil J. Rheumatic heart disease: proinflammatory cytokines play a role in the progression and maintenance of valvular lesions. Am J Pathol. 2004;165(5):1583-91.
Chen MC, Chang HW, Wu CJ, Yang CH, Yu TH, Chen CJ, Hung WC. Balance between plasma levels of tumor necrosis factor-alpha and interleukin-10 in rheumatic mitral stenosis. Cardiology. 2005;104(4):171-5.
Chang CJ, Hsu LA, Chiang CW, Ko YS, See LC, Shen YC, Ko YL, Kou CT, Lee YS, Pang JH. Percutaneous transvenous mitral valvulotomy normalizes elevated circulating levels of tumor necrosis factor-alpha and interleukin-6 in mitral stenosis with heart failure. Am J Cardiol. 2003;91(8):1018-20.