Advertisement

Clinical and Experimental Medicine

, Volume 19, Issue 1, pp 87–92 | Cite as

Association between IL-35 and coronary arterial lesions in children with Kawasaki disease

  • Ya Su
  • Siqi Feng
  • Li Luo
  • Ruixi LiuEmail author
  • Qijian YiEmail author
Original Article
  • 329 Downloads

Abstract

Kawasaki disease (KD) arises due to the acute inflammation and immune system dysfunction. This study investigated the relationship between the serum level of IL-35 and coronary artery lesions (CALs) in patients with KD. We obtained blood samples from 90 children with KD before intravenous immunoglobulin therapy. Levels of IL-35, IL-6, IL-17A, IL-10, MCP-1 and VEGF were measured in 190 cases, including 4 groups: KD with coronary arterial lesions (n = 46), KD without coronary arteries lesions (n = 44), febrile control group (FC, n = 40) and the normal control group (NC, n = 60). White blood cell counts (WBC), red blood cell counts (RBC), hemoglobin, platelet, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and procalcitonin were tested in all subjects. Levels of IL-35, RBC and hemoglobin significantly decreased, and IL-6, IL-17A, IL-10, MCP-1 and VEGF were significantly elevated in the KD group compared with febrile and control groups. IL-35 serum level even decreased, and ESR, IL-6, MCP-1 and VEGF increased in the KD patients with CALs. Serum levels of IL-35 in KD patients were negatively associated with WBC, CRP, IL-6, IL-17A, IL-10, MCP-1 and VEGF in children with KD. IL-35 may have the effect on inhibiting inflammatory process in KD and further preventing KD patients from coronary artery lesion.

Keywords

Kawasaki disease (KD) Interleukin-35 (IL-35) Interleukin-17A (IL-17A) Interleukin-10 (IL-10) Coronary arterial lesion 

Notes

Acknowledgements

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

Compliance with ethical standards

Conflict of interest

All authors have no actual or potential conflicts of interest with other people or organizations to this work.

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.

References

  1. 1.
    Kawasaki T, Kosaki F, Okawa S, et al. A new infantile acute febrile mucocutaneous lymph node syndrome (MCLS) prevailing in Japan. Pediatrics. 1974;54:271–6.Google Scholar
  2. 2.
    Kato H, Koike S, Yamamoto M, et al. Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome. J Pediatr. 1975;86:892–8.CrossRefGoogle Scholar
  3. 3.
    Rowley AH, Shulman ST. Pathogenesis and management of Kawasaki disease. Expert Rev Anti Infect Ther. 2010;8:197–203.CrossRefGoogle Scholar
  4. 4.
    Burns JC, Glode MP. Kawasaki syndrome. Lancet. 2004;364:533–44.CrossRefGoogle Scholar
  5. 5.
    Guo MMH, Tseng WN, Ko CH, et al. Th17- and Treg-related cytokine and mRNA expression are associated with acute and resolving Kawasaki disease. Allergy. 2015;70:310–8.CrossRefGoogle Scholar
  6. 6.
    Cumming C, McCartyh P, van Hoff J, et al. Kawasaki disease associated with reactive hemophagocytic lymphohistiocytosis. Pediatr Infect Dis J. 2008;27(12):1116–8.CrossRefGoogle Scholar
  7. 7.
    Collison LW, Workman CJ, Kuo TT, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature. 2007;450:566–9.CrossRefGoogle Scholar
  8. 8.
    Kempe S, Heinz P, Kokai E, et al. Epsteinbarr virus-induced gene-3 is expressed in human atheroma plaques. Am J Pathol. 2009;175:440–7.CrossRefGoogle Scholar
  9. 9.
    Li X, Mai J, Virtue A, et al. IL-35 is a novel responsive antiinflammatory cytokine—a new system of categorizing anti-inflammatory cytokines. PLoS ONE. 2012;7:e33628.CrossRefGoogle Scholar
  10. 10.
    Bettini M, Castellaw AH, Lennon GP, et al. Prevention of autoimmune diabetes by ectopic pancreatic β-cell expression of interleukin-35. Diabetes. 2012;61:1519–26.CrossRefGoogle Scholar
  11. 11.
    Chaturvedi V, Collison LW, Guy CS, et al. Cutting edge: human regulatory T cells require IL-35 to mediate suppression and infectious tolerance. J Immunol. 2011;186:6661–6.CrossRefGoogle Scholar
  12. 12.
    Niedbala W, Wei XQ, Cai B, et al. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur J Immunol. 2007;37:3021–9.CrossRefGoogle Scholar
  13. 13.
    Lin Y, Huang Y, Lu Z, et al. Decreased plasma IL-35 levels are related to the left ventricular ejection fraction in coronary artery diseases. PLoS ONE. 2012;7(12):e52490.CrossRefGoogle Scholar
  14. 14.
    JCS Joint Working Group. Guidelines for diagnosis and management of cardiovascular sequelae in Kawasaki disease (JCS 2008). Circ J. 2010;74:1989–2020.CrossRefGoogle Scholar
  15. 15.
    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
  16. 16.
    Wirtz S, Billmeier U, Mchedlidze T, et al. Interleukin-35 mediates mucosal immune responses that protect against T-cell-dependent colitis. Gastroenterology. 2011;141(5):1875–86.CrossRefGoogle Scholar
  17. 17.
    Zandian M, Mott KR, Allen SJ, et al. Use of cytokine immunotherapy to block CNS demyelination induced by a recombinant HSV-1 expressing IL-2. Gene Ther. 2011;18:734–42.CrossRefGoogle Scholar
  18. 18.
    Huang CH, Loo EX, Kuo IC, et al. Airway inflammation and IgE production induced by dust mite allergen-specific memory/effector Th2 cell line can be effectively attenuated by IL-35. J Immunol. 2011;187:462–71.CrossRefGoogle Scholar
  19. 19.
    Workman CJ, Szymczak-Workman AL, Collison LW, et al. The development and function of regulatory T cells. Cell Mol Life Sci. 2009;66:2603–22.CrossRefGoogle Scholar
  20. 20.
    Crome SQ, Wang AY, Levings MK. Translational mini-review series on Th17 cells: function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol. 2010;159:109–19.CrossRefGoogle Scholar
  21. 21.
    Jia S, Li C, Wang G, et al. The T helper type 17/regulatory T cell imbalance in patients with acute Kawasaki disease. Clin Exp Immunol. 2010;162:131–7.CrossRefGoogle Scholar
  22. 22.
    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.Google Scholar
  23. 23.
    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.CrossRefGoogle Scholar
  24. 24.
    Nakano S, Morimoto S, Suzuki S, et al. Immunoregulatory role of IL-35 in T cells of patients with rheumatoid arthritis. Rheumatology (Oxford). 2015;54:1498–506.CrossRefGoogle Scholar
  25. 25.
    Yang J, Yang M, Htut TM, et al. Epstein-Barr virus-induced gene 3 negatively regulates IL-17, IL-22 and ROR gamma t. Eur J Immunol. 2008;38:1204–14.CrossRefGoogle Scholar
  26. 26.
    Lalani I, Bhol K, Ahmed AR. Interleukin-10: biology, role in inflammation and autoimmunity. Ann Allergy Asthma Immunol. 1997;79(6):469–83.CrossRefGoogle Scholar
  27. 27.
    Kochetkova I, Golden S, Holderness K, et al. IL-35 stimulation of CD39 + regulatory T cells confers protection against collagen II-induced arthritis via the production of IL-10. J Immunol. 2010;184:7144–53.CrossRefGoogle Scholar
  28. 28.
    Leonard EJ, Yoshimura T. Human monocyte chemoattractant protein-1 (MCP-1). Immunol Today. 1990;11:97–101.CrossRefGoogle Scholar
  29. 29.
    Matsushima K, Larsen CG, Dubois GC, et al. Purification and characterization of a novel monocyte chemotactic and activating actor produced by a human myelomonocytic cell line. J Exp Med. 1985;169:1485–90.CrossRefGoogle Scholar
  30. 30.
    Terai M, Jibiki T, Harada A, et al. Dramatic decrease of circulating levels of monocyte chemoattractant protein-1 in kawasaki disease after gamma globulin treatment. J Leukoc Biol. 1999;65:566–72.CrossRefGoogle Scholar
  31. 31.
    Asano T, Ogawa S. Expression of monocyte chemoattractant protein-1 in Kawasaki disease: the anti-inflammatory effect of gamma globulin therapy. Scand J Immunol. 2000;51(1):98–103.CrossRefGoogle Scholar
  32. 32.
    Filková M, Vernerová Z, Hulejová H, et al. Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis. Cytokine. 2015;73:36–43.CrossRefGoogle Scholar
  33. 33.
    Koyanagi H, Nakayama Y, Yanagawa H. Lower level of serum potassium and higher level of C-reactive protein as an independent risk factor for giant aneurysms in Kawasaki disease. Acta Paediatr. 1998;87:32–6.CrossRefGoogle Scholar
  34. 34.
    Connolly DT, Heuvelman DM, Nelson R, et al. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest. 1989;84:1470–8.CrossRefGoogle Scholar
  35. 35.
    Leung DYW, Cachianes G, Kuang W-J, et al. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989;246:1306–9.CrossRefGoogle Scholar
  36. 36.
    Ohno T, Yuge T, Kariyazono H, et al. Serum hepatocyte growth factor combined with vascular endothelial growth factor as a predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease. Eur J Pediatr. 2002;161:105–11.CrossRefGoogle Scholar
  37. 37.
    Hamamichi Y, Ichida F, Yu X, et al. Neutrophils and mononuclear cells express vascular endothelial growth factor in acute Kawasaki disease: its possible role in progression of coronary artery lesions. Pediatr Res. 2001;49:74–80.CrossRefGoogle Scholar
  38. 38.
    Suqin W, Li Y, Li Y. Interleukin-35 attenuates collagen-induced arthritis through suppression of vascular endothelial growth factor and its receptors. Int Immunopharmacol. 2016;34:71–7.CrossRefGoogle Scholar
  39. 39.
    Jiang S, Li Y, Lin T, et al. IL-35 inhibits angiogenesis through VEGF/Ang2/Tie2 pathway in rheumatoid arthritis. Cell Physiol Biochem. 2016;40:1105–16.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018
Corrected Publication October 2018

Authors and Affiliations

  1. 1.Key Laboratory of Pediatrics in ChongqingChongqingChina
  2. 2.China International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqingChina
  3. 3.Department of Cardiovascular MedicineChildren’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and DisorderChongqingChina

Personalised recommendations