TY - JOUR
T1 - Inflammatory cytokine profiles during Cyclosporin treatment for immunoglobulin-resistant Kawasaki disease
AU - Hamada, Hiromichi
AU - Suzuki, Hiroyuki
AU - Abe, Jun
AU - Suzuki, Yoichi
AU - Suenaga, Tomohiro
AU - Takeuchi, Takashi
AU - Yoshikawa, Norishige
AU - Shibuta, Shoichi
AU - Miyawaki, Masakazu
AU - Oishi, Ko
AU - Yamaga, Hironobu
AU - Aoyagi, Noriyuki
AU - Iwahashi, Seiji
AU - Miyashita, Ritsuko
AU - Honda, Takafumi
AU - Onouchi, Yoshihiro
AU - Terai, Masaru
AU - Hata, Akira
N1 - Funding Information:
This work was supported by a Grant-in-Aid from the Ministry of Health, Labour and Welfare, Japan.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
KW - Cyclosporine
KW - IL-6
KW - Immunoglobulin
KW - Kawasaki disease
KW - Soluble IL-2 receptor
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U2 - 10.1016/j.cyto.2012.08.006
DO - 10.1016/j.cyto.2012.08.006
M3 - Article
C2 - 22944461
AN - SCOPUS:84867997010
VL - 60
SP - 681
EP - 685
JO - Cytokine
JF - Cytokine
SN - 1043-4666
IS - 3
ER -