Inflammatory cytokine profiles during Cyclosporin treatment for immunoglobulin-resistant Kawasaki disease

Hiromichi Hamada, Hiroyuki Suzuki, Jun Abe, Yoichi Suzuki, Tomohiro Suenaga, Takashi Takeuchi, Norishige Yoshikawa, Shoichi Shibuta, Masakazu Miyawaki, Ko Oishi, Hironobu Yamaga, Noriyuki Aoyagi, Seiji Iwahashi, Ritsuko Miyashita, Takafumi Honda, Yoshihiro Onouchi, Masaru Terai, Akira Hata

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Background: Kawasaki disease (KD) is an acute systemic vasculitis occurring in medium-sized arteries, especially coronary arteries. Patients with KD who fail to respond to standard therapy with intravenous immunoglobulin (IVIG) face a higher risk of developing coronary artery lesions. Cyclosporin A (CsA) is one treatment option for IVIG-resistant KD. However, the mechanism of its suppression of inflammation in patients with KD remains unknown. Methods and results: We analyzed time-line profiles of multiple inflammatory cytokines in sera of 19 patients treated with CsA (4. mg/kg/day, p.o., 14 days) after additional IVIG. Trough concentration of CsA in blood was maintained between 60 and 200. ng/ml. We examined serum samples before, on day 7, and at the end (day 14) of CsA treatment. Assays were conducted using a Milliplex kit®. Fourteen patients responded to CsA and became afebrile within 5 days (Responders), although five patients were regarded as Non-responders. Serum transitional levels of IL-6 (p<0.001), sIL-2R (p<0.001), sTNFRII (p<0.001), and G-CSF (p<0.001) reflect disease severity. In Non-responders, average levels of IL-6 at day 7 (43.5 vs. 13.8. pg/ml, p<0.001) and average levels of sIL-2R at day 14 (21.3 vs. 3.31. pg/ml, p=0.014) were significantly higher than those in Responders. Conclusion: CsA treatment effectively reduced the persisting serum inflammatory cytokines in most of the IVIG-resistant KD patients. Soluble IL-2R suppression implies a mechanism explaining the effects of CsA.

Original languageEnglish
Pages (from-to)681-685
Number of pages5
JournalCytokine
Volume60
Issue number3
DOIs
Publication statusPublished - 2012 Dec

Keywords

  • Cyclosporine
  • IL-6
  • Immunoglobulin
  • Kawasaki disease
  • Soluble IL-2 receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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