Increased Levels of IL-23 in Peripheral Blood Mononuclear Cells of Patients With Chronic Heart Failure

  • Vajiheh Eskandari Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  • Ali Akbar Amirzargar Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Molecular Immunology Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
  • Bobak Moazzami Student Research Committee, Babol University of Medical Sciences, Babol, Iran. AND Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
  • Mohammad Jafar Mahmoudi Department of Cardiology, Amir Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran.
  • Zahra Rahnemoon Cardiac Heart Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  • Samaneh Sadati Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  • Zahra Rahmati Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  • Fatemeh Gorzin Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  • Mona Hedayat Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. AND Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Boston, MA, USA.
  • Nima Rezaei Mail Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. AND Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Sheffield, UK.
Keywords:
Heart failure, Cytokines, Gene expression, Immunology

Abstract

Chronic heart failure (CHF) is a complex clinical syndrome that represents the end stage of various cardiac diseases and is characterized by the inability of the heart to meet metabolic demands of the body. Many physiological systems are involved in this disease. In particular, the activation of the immune system has received considerable interest in the last decade. Evidence from both experimental and clinical trials indicates that inflammatory mediators are of importance in the pathogenesis and progression of chronic heart failure. Excessive pro-inflammatory cytokines induce contractile dysfunction, hypertrophy, and fibrosis and cell death in Cardiac myocyte. We examined the expression of IL-23 in PBMCs between CHF patients and healthy controls. In this report, we used real-time PCR assay to compare the relative expression of IL-23 in peripheral blood mononuclear cells (PBMC) from CHF patients with various heart diseases (n=42, EF<45%, range of New York Heart Association (NYHA) 1 to 4) and matched healthy control subjects (n=42).We also determined the IL-23 concentrations of cell culture supernatant of PBMCs with ELISA. A total of 42 patients with CHF, with 42 age and sex-matched control group subjects were enrolled in the present study. The culture supernatant levels of IL-23 in PBMC of CHF patients were significantly higher (133.95±108.99 pg/mL) than in the control group (83.43±76.2 pg/mL) (P<0.05). The gene expression of IL-23 was also markedly upregulated in PBMC from CHF patients in comparison with the control group, but it was not statically significant 80. These results demonstrate that in patients with CHF and especially those with severe CHF, expression of pro-inflammatory cytokines and levels of IL-23 cytokine is markedly increased in PBMC. These finding suggested that IL-23 may play an important role in the progression of CHF among these patients.

References

Riegel, B., et al., Heart failure self-care in developed and developing countries. J Card Fail, 2009. 15(6): p. 508-16.

Remme, W.J. and K. Swedberg, Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J, 2001. 22(17): p. 1527-60.

Francis, G.S., et al., The neurohumoral axis in congestive heart failure. Ann Intern Med, 1984. 101(3): p. 370-7.

Packer, M., Neurohormonal interactions and adaptations in congestive heart failure. Circulation, 1988. 77(4): p. 721-30.

Remes, J., et al., Neuroendocrine activity in untreated heart failure. Br Heart J, 1991. 65(5): p. 249-55.

Cohn, J.N., et al., Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med, 1984. 311(13): p. 819-23.

Hedayat, M., et al., Proinflammatory cytokines in heart failure: double-edged swords. Heart Fail Rev, 2010. 15(6): p. 543-62.

Satoh, M., et al., Increased expression of tumor necrosis factor-alpha converting enzyme and tumor necrosis factor-alpha in peripheral blood mononuclear cells in patients with advanced congestive heart failure. Eur J Heart Fail, 2004. 6(7): p. 869-75.

Zhao, S.P. and T.D. Xu, Elevated tumor necrosis factor alpha of blood mononuclear cells in patients with congestive heart failure. Int J Cardiol, 1999. 71(3): p. 257-61.

Mann, D.L., Inflammatory mediators and the failing heart: past, present, and the foreseeable future. Circ Res, 2002. 91(11): p. 988-98.

El-Menyar, A.A., Cytokines and myocardial dysfunction: state of the art. J Card Fail, 2008. 14(1): p. 61-74.

Petersen, J.W. and G.M. Felker, Inflammatory biomarkers in heart failure. Congest Heart Fail, 2006. 12(6): p. 324-8.

Pudil, R., et al., Cytokines and adhesion molecules in the course of acute myocardial infarction. Clin Chim Acta, 1999. 280(1-2): p. 127-34.

Chomczynski, P. and N. Sacchi, Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem, 1987. 162(1): p. 156-9.

Matsumori, A., et al., Increased circulating cytokines in patients with myocarditis and cardiomyopathy. Br Heart J, 1994. 72(6): p. 561-6.

Tsutamoto, T., et al., Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J Am Coll Cardiol, 1998. 31(2): p. 391-8.

Fedacko, J., et al., Inflammatory mediators in chronic heart failure in North India. Acta Cardiol, 2014. 69(4): p. 391-8.

Pignatelli, P., et al., Tumor necrosis factor-alpha as trigger of platelet activation in patients with heart failure. Blood, 2005. 106(6): p. 1992-4.

Chandrashekhar, Y., Role of apoptosis in ventricular remodeling. Curr Heart Fail Rep, 2005. 2(1): p. 18-22.

Erbel, C., et al., Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability. Basic Res Cardiol, 2011. 106(1): p. 125-34.

Lajoie, S., et al., Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nat Immunol, 2010. 11(10): p. 928-35.

Sutton, C.E., et al., Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity, 2009. 31(2): p. 331-41.

Cai, Y., et al., Pivotal role of dermal IL-17-producing gammadelta T cells in skin inflammation. Immunity, 2011. 35(4): p. 596-610.

Chen, Y. and K.J. Wood, Interleukin-23 and TH17 cells in transplantation immunity: does 23+17 equal rejection? Transplantation, 2007. 84(9): p. 1071-4.

Abbas, A., et al., Interleukin 23 levels are increased in carotid atherosclerosis: possible role for the interleukin 23/interleukin 17 axis. Stroke, 2015. 46(3): p. 793-9.

Liao, Y.H., et al., Interleukin-17A contributes to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and neutrophil infiltration. J Am Coll Cardiol, 2012. 59(4): p. 420-9.

Barry, S.P., et al., Enhanced IL-17 signalling following myocardial ischaemia/reperfusion injury. Int J Cardiol, 2013. 163(3): p. 326-34.

Nakae, S., et al., Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity, 2002. 17(3): p. 375-87.

Yan, X., et al., Deleterious effect of the IL-23/IL-17A axis and gammadeltaT cells on left ventricular remodeling after myocardial infarction. J Am Heart Assoc, 2012. 1(5): p. e004408.

Published
2018-05-20
How to Cite
1.
Eskandari V, Amirzargar AA, Moazzami B, Mahmoudi MJ, Rahnemoon Z, Sadati S, Rahmati Z, Gorzin F, Hedayat M, Rezaei N. Increased Levels of IL-23 in Peripheral Blood Mononuclear Cells of Patients With Chronic Heart Failure. Acta Med Iran. 56(5):295-300.
QRcode
Section
Original Article(s)