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Inflammation-Induced Hepcidin is Associated with the Development of Anemia and Coronary Artery Lesions in Kawasaki Disease

Journal of Clinical Immunology volume 32, pages 746–752 (2012)Cite this article

Abstract

Purpose

Kawasaki disease (KD) is a systemic febrile vasculitis complicated by coronary artery lesions (CAL). Anemia is common in patients with KD and is associated with a prolonged duration of active inflammation. Hepcidin is a central modulator of inflammation-associated anemia, acting via control of iron absorption and a direct inhibitory effect on erythropoiesis. The aims of this study were to investigate the role of inflammation-induced hepcidin in the development of anemia, the occurrence of CAL formation, and IVIG treatment response in patients with KD.

Methods

Eighty-six KD patients and 30 febrile controls were enrolled. Levels of interleukin (IL)-6 and serum hepcidin were measured in sera by enzyme-linked immunosorbent assay. Hemoglobin and serum iron levels were also measured.

Results

Hemoglobin and iron levels were lower in KD patients than in controls (p < 0.001 and p = 0.009, respectively). Serum hepcidin and IL-6 levels were higher in KD patients than in controls (both p < 0.001) before intravenous immunoglobulin (IVIG) treatment. After IVIG treatment, serum hepcidin, IL-6, and hemoglobin levels decreased significantly (all p < 0.001). In addition, the serum hepcidin levels before IVIG treatment were negatively correlated with hemoglobin levels after IVIG treatment (R = −0.188, p = 0.046) and positively correlated with the changes of hemoglobin levels after IVIG treatment (R = 0.269, p = 0.015). Furthermore, serum hepcidin levels were negatively correlated with serum iron levels (R = −0.412, p = 0.002), which were positively correlated with hemoglobin levels (R = 0.210, p = 0.045). Additionally, the change of hepcidin levels was associated with IVIG treatment response and the occurrence of CAL formation.

Conclusions

Inappropriately raised hepcidin levels impair iron metabolism and are associated with decreased hemoglobin levels in KD patients. Inflammation-induced hepcidin is associated with the development of anemia and disease outcomes in patients with KD.

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Acknowledgments

This study was supported by grants from the National Science Council Grant #NSC 99-2314-B-182A-032-MY2, NSC 100-2314-B-182A-048-MY3, and Chang Gung Memorial Hospital CMRPG8A021, Taiwan.

Conflicts of Interest

The authors have indicated that they have no financial relationships relevant to this article to disclose.

Author information

Affiliations

  1. Genomic and Proteomic Core Laboratory, Department of Medical Research and Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China

    Ho-Chang Kuo

  2. Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China

    Mao-Meng Tiao, Hong-Ren Yu, Li-Tung Huang, Chiu-Ping Lee & Ying-Hsien Huang

  3. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China

    Ya-Ling Yang

  4. Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China

    Jiin-Haur Chuang

  5. Department of Medical Research, Show Chwan Memorial Hospital in Chang Bing, Changhua, Taiwan, Republic of China

    Kuender D. Yang

  6. Department of Medical Genetics, Kaohsiung Medical University, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China

    Wei-Chiao Chang

Authors
  1. Ho-Chang Kuo
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  2. Ya-Ling Yang
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  7. Kuender D. Yang
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  8. Wei-Chiao Chang
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  9. Chiu-Ping Lee
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  10. Ying-Hsien Huang
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Corresponding author

Correspondence to Ying-Hsien Huang.

Additional information

Ho-Chang Kuo and Ya-Ling Yang contributed equally to this work.

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Kuo, HC., Yang, YL., Chuang, JH. et al. Inflammation-Induced Hepcidin is Associated with the Development of Anemia and Coronary Artery Lesions in Kawasaki Disease. J Clin Immunol 32, 746–752 (2012). https://doi.org/10.1007/s10875-012-9668-1

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  • DOI: https://doi.org/10.1007/s10875-012-9668-1

Keywords

  • Coronary artery lesion
  • hemoglobin
  • hepcidin
  • IL-6
  • iron
  • Kawasaki disease