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Relationship between IL-27 and coronary arterial lesions in children with Kawasaki disease

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Abstract

Kawasaki disease (KD) arises due to the disorder of the inflammation response and faulty immune regulation. Interleukin-27 (IL-27) is a novel cytokine with both pro-inflammatory and anti-inflammatory effects. This study investigated the relationship between serum levels of IL-27, Interleukin-17A (IL-17A), Interleukin-10 (IL-10), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and coronary artery lesions (CALs) in patients with KD. We obtained blood samples from 81 children with KD before intravenous immunoglobulin (IVIG) therapy. Levels of IL-27, IL-17A, IL-10, IL-6, IL-1β and TNF-α were measured in 251 cases, including 4 groups: the normal control group, NC (n = 90), febrile control, FC (n = 80), KD without coronary arteries (n = 41) and KD with coronary arterial lesions (n = 40). White blood cells counts (WBC), red blood cells counts (RBC), hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate and procalcitonin (PCT) were tested in all subjects. Levels of IL-27, IL-10, IL-17A, IL-6, IL-1β and TNF-α were significantly elevated, and RBC and hemoglobin significantly decreased in the group of KD group compared with febrile and control groups. IL-27, IL-6, IL-1β and TNF-α serum levels are even higher in KD children with CALs. There was positive relationship between serum levels of IL-27 and WBC, CRP, PCT, IL-10, IL-17A, IL-6 and TNF-α in children with KD. The up-regulation of IL-27 may be closely linked to up-regulation of systemic pro-inflammatory markers in acute KD. Morover, IL-27 may be involved in the development of CALs in acute KD.

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References

  1. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children: clinical observations of 50 cases. Jpn J Allerg. 1967;16:178–222.

    CAS  Google Scholar 

  2. Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics. 2004;114:1708–33.

    Article  PubMed  Google Scholar 

  3. Yeung RS. Kawasaki disease: update on pathogenesis. Curr Opin Rheumatol. 2010;22:551–60.

    Article  PubMed  Google Scholar 

  4. Settin A, Ismail A, El-Magd MA, et al. Gene polymorphisms of TNF-alpha-308 (G/A), IL-10 (-1082) (G/A), IL-6 (-174) (G/C) and IL-1Ra (VNTR) in Egyptian cases with type 1 diabetes mellitus. Autoimmunity. 2009;42:50–5.

    Article  CAS  PubMed  Google Scholar 

  5. Afzali B, Lombardi G, Lechler RI, et al. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exp Immunol. 2007;148:32–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pflanz S, Timans JC, Cheung J, et al. IL-27, a heterodi-meric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. Immunity. 2002;16:779–90.

    Article  CAS  PubMed  Google Scholar 

  7. Boulay JL, O’Shea JJ, Paul WE, et al. Molecular phylogeny within type I cytokines and their cognate receptors. Immunity. 2003;19(2):159–63.

    Article  CAS  PubMed  Google Scholar 

  8. Lin TT, Lu J, Qi CY, et al. Elevated serum level of IL-27 and VEGF in patients with ankylosing spondylitis and associate with disease activity. Clin Exp Med. 2015;15(2):227–31.

    Article  CAS  PubMed  Google Scholar 

  9. Seita J, Asakawa M, Ooehara J, et al. Interleukin-27 directly induces differentiation in hematopoietic stem cells. Blood. 2008;111(4):1903–12.

    Article  CAS  PubMed  Google Scholar 

  10. Park JS, Jung YO, Oh HJ, et al. Interleukin-27 suppresses osteoclastogenesis via induction of interferon-γ. Immunology. 2012;137(4):326–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hunter CA, Kastelein R. Interleukin-27: balancing protective and pathological immunity. Immunity. 2012;37:960–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wong Hector R, Cvijanovich Natalie Z, Hall Mark, et al. Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children. Crit Care. 2012;16:R213.

    Article  PubMed  PubMed Central  Google Scholar 

  13. JCS Joint Working Group. Guidelines for diagnosis and management of cardiovascular sequelae in Kawasaki disease (JCS 2008). Circ J. 2010;74:1989–2020.

    Article  Google Scholar 

  14. Japan Kawasaki Disease Research Committee. Report of subcommittee on standardization of diagnostic criteria and reporting of coronary artery lesions in Kawasaki disease. Tokyo: Ministry of Health and Welfare; 1984.

    Google Scholar 

  15. Rowley AH, Shulman ST. Pathogenesis and management of Kawasaki disease. Expert Rev Anti Infect Ther. 2010;8:197–203.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Liu R, He B, Gao F, et al. Relationship between adipokines and coronary artery aneurysm in children with Kawasaki disease. Transl Res. 2012;160:131–6.

    Article  CAS  PubMed  Google Scholar 

  17. Hirao J, Hibi S, Andoh T, Ichimura T. High levels of circulating interleukin-4 and interleukin-10 in Kawasaki disease. Int Arch Allergy Immunol. 1997;112:152–6.

    Article  CAS  PubMed  Google Scholar 

  18. Guo MM-H, Tseng W-N, Ko C-H, et al. Th17- and Treg-related cytokine and mRNA expression are associated with acute and resolving Kawasaki disease. Allergy. 2015;70:310–8.

    Article  CAS  PubMed  Google Scholar 

  19. Maddur MS, Sharma M, et al. Inhibitory Effect of IVIG on IL-17 production by Th17 Cells is Independent of Anti-IL-17 antibodies in the Immunoglobulin Preparations. J Clin Immunol. 2013;33:S62–6.

    Article  PubMed  Google Scholar 

  20. Maddura Mohan S, Kaveri Srini V, Bayry Jagadeesh. Comparison of different IVIg preparations on IL-17 production by human Th17 cells. Autoimmun Rev. 2011;10:809–10.

    Article  Google Scholar 

  21. Maddur MS, Hegde P, et al. Inhibition of differentiation, amplification, and function of human TH17 cells by intravenous immunoglobulin. J Allergy Clin Immunol. 2011;127(3):823–30.

    Article  CAS  PubMed  Google Scholar 

  22. Rasouli Manoochehr, Heidarib Behzad, Kalani Mehdi, et al. Downregulation of Th17 cells and the related cytokines with treatment in Kawasaki disease. Immunol Lett. 2014;162:269–75.

    Article  CAS  PubMed  Google Scholar 

  23. Yoshida H, Nakaya M, Miyazaki Y. Interleukin 27: a double-edged sword for offense and defense. J Leukoc Biol. 2009;86:1295–303.

    Article  CAS  PubMed  Google Scholar 

  24. Wirtz S, Tubbe I, Galle PR, et al. Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27. J Exp Med. 2006;203:1875–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Niedbala W, Cai B, Wei X, et al. Interleukin 27 attenuates collagen-induced arthritis. Ann Rheum Dis. 2008;67:1474–9.

    Article  CAS  PubMed  Google Scholar 

  26. Ma Ming-Chieh, Bao-Wei WangTzu-Pei Yeh, et al. Interleukin-27, a novel cytokine induced by ischemia–reperfusion injury in rat hearts, mediatescardioprotective effectsvia the gp130/STAT3 pathway. Basic Res Cardiol. 2015;110:22.

    Article  PubMed  Google Scholar 

  27. Yoshimoto T, Yoshimoto T, Yasuda K, et al. IL-27 suppresses Th2 cell development and Th2 cytokines production from polarized Th2 cells: a novel therapeutic way for Th2-mediated allergic inflammation. J Immunol. 2007;179(7):4415–23.

    Article  CAS  PubMed  Google Scholar 

  28. Lai X, Wang H, Cao J, et al. Circulating IL-27 is elevated in rheumatoid arthritis patients. Molecules. 2016;21(11):1565.

    Article  Google Scholar 

  29. Stumhofer JS, Laurence A, Wilson EH, et al. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol. 2006;7:937–45.

    Article  CAS  PubMed  Google Scholar 

  30. Wang H, Meng R, Li Z, et al. IL-27 induces the differentiation of Tr1-like cells from human naive CD4+ T cells via the phosphorylation of STAT1 and STAT3. Immunol Lett. 2011;136:21–8.

    Article  CAS  PubMed  Google Scholar 

  31. Jia S, Li C, Wang G, et al. The T helper type 17/regulatory T cell imbalance in patients with acute Kawasaki diseasec. Clin Exp Immunol. 2010;162:131–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kobayashi N, Mori M, Kobayashi Y, et al. Intravenous gamma-globulin therapy improves hypercytokinemia in the acute phase of Kawasaki disease. Mod Rheumatol. 2004;14:447–52.

    Article  CAS  PubMed  Google Scholar 

  33. Lalani I, Bhol K, Ahmed AR. Interleukin-10: biology, role in inflammation and autoimmunity. Ann Allergy Asthma Immunol. 1997;79:469–83.

    Article  CAS  PubMed  Google Scholar 

  34. CromeSQ WangAY. LevingsMK. Translationalmini-reviewseries on Th17 cells: function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol. 2010;159:109–19.

    Article  Google Scholar 

  35. Laan M, Cui ZH, Hoshino H, et al. Neutrophil recruitment by human IL- 17 via C-X-C chemokine release in the airways. J Immunol. 1999;162:2347–52.

    CAS  PubMed  Google Scholar 

  36. Afzali B, Mitchell P, Lechler RI, et al. Translational mini-review series on Th17 cells: induction of interleukin-17 production by regulatory T cells. Clin Exp Immunol. 2010;159:120–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Volin MV, Shahrara S. Role of TH-17 cells in rheumatic and other autoimmune diseases. Rheumatology (Sunnyvale). 2011. doi:10.4172/2161-1149.1000104.

  38. Tang SC, Fan XH, Pan QM, et al. Decreased expression of IL-27 and its correlation with Th1 and Th17 cells in progressive multiple sclerosis. J Neurol Sci. 2015;348(1–2):174–80.

    Article  CAS  PubMed  Google Scholar 

  39. Yoshikawa H, Nomura Y, Masuda K, et al. Serum procalcitonin value is useful for predicting severity of Kawasaki disease. Pediatr Infect Dis J. 2012;31(5):523–5.

    Article  PubMed  Google Scholar 

  40. Pietraforte Donatella, Gambardella Lucrezia, Marchesi Alessandra, et al. Red blood cells as bioindicators of cardiovascular risk in Kawasaki disease: a case report. Int J Cardiol. 2015;181:311–3.

    Article  PubMed  Google Scholar 

  41. Straface E, Gambardella L, Metere A, et al. Oxidative stress and defective platelet apoptosis in naïve patient with Kawasaki disease. Biochem Biophys Res Commun. 2010;392:426–30.

    Article  CAS  PubMed  Google Scholar 

  42. Galeotti C, Kaveri SV, Cimaz R, et al. Predisposing factors, pathogenesis and therapeutic intervention of Kawasaki disease. Drug Discov Today. 2016;21(11):1850–7.

    Article  CAS  PubMed  Google Scholar 

  43. Newburger JW, et al. Kawasaki disease. J Am Coll Cardiol. 2016;67(14):1738–49.

    Article  PubMed  Google Scholar 

  44. Galeotti C, Kaveri SV, Bayry Jagadeesh. Molecular and immunological biomarkers to predict IVIg response. Trends Mol Med. 2015;21(3):145–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by National Natural Science Foundation of China under Grant: No. 81270412 and National Natural Science Foundation of China under Grant: No. 81500273.

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Authors and Affiliations

  1. Key Laboratory of Pediatrics in Chongqing, Chongqing, 400014, People’s Republic of China

    Feifei Si, Yao Wu, Fang Gao & Siqi Feng

  2. Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, 400014, People’s Republic of China

    Feifei Si, Yao Wu, Fang Gao & Siqi Feng

  3. Department of Cardiovascular Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China

    Ruixi Liu & Qijian Yi

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  1. Feifei Si
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  2. Yao Wu
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Correspondence to Ruixi Liu or Qijian Yi.

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All authors have no actual or potential conflicts of interest with other people or organizations with 3 years of initiating the work presented here.

Ethical approval

The study protocol was approved by the Ethics Committee of Children’s Hospital of Chongqing Medicine University, and written informed consent forms were obtained from the parents of all subjects.

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Si, F., Wu, Y., Gao, F. et al. Relationship between IL-27 and coronary arterial lesions in children with Kawasaki disease. Clin Exp Med 17, 451–457 (2017). https://doi.org/10.1007/s10238-017-0451-8

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  • DOI: https://doi.org/10.1007/s10238-017-0451-8

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