title: Inflammatory cytokine profiles during Cyclosporin treatment for immunoglobulin-resistant Kawasaki disease.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan. h-hamada@tymc.twmu.ac.jp
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Hamada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Jun
authors.initials: J
authors.lastname: Abe
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Suenaga
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Norishige
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: Shoichi
authors.initials: S
authors.lastname: Shibuta
authors.forename: Masakazu
authors.initials: M
authors.lastname: Miyawaki
authors.forename: Ko
authors.initials: K
authors.lastname: Oishi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yamaga
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Aoyagi
authors.forename: Seiji
authors.initials: S
authors.lastname: Iwahashi
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Miyashita
authors.forename: Takafumi
authors.initials: T
authors.lastname: Honda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Onouchi
authors.forename: Masaru
authors.initials: M
authors.lastname: Terai
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
mesh_terms: D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007167:Immunotherapy; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D016572:Cyclosporine