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

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• 作者：Hiromichi Hamada^a ; ^{h-hamada@tymc.twmu.ac.jp} ; Hiroyuki Suzuki^b ; Jun Abe^c ; Yoichi Suzuki^d ; Tomohiro Suenaga^b ; Takashi Takeuchi^b ; Norishige Yoshikawa^b ; Shoichi Shibuta^e ; Masakazu Miyawaki^e ; Ko Oishi^f ; Hironobu Yamaga^g ; Noriyuki Aoyagi^h ; Seiji Iwahashiⁱ ; Ritsuko Miyashita^j ; Takafumi Honda^a ; Yoshihiro Onouchi^d ; Masaru Terai^a ; Akira Hata^d
• 关键词：Kawasaki disease ; Cyclosporine ; Soluble IL-2 receptor ; IL-6 ; Immunoglobulin
• 刊名：Cytokine
• 出版年：2012
• 出版时间：December, 2012
• 年：2012
• 卷：60
• 期：3
• 页码：681-685
• 全文大小：393 K

文摘

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.