title: Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki disease.
abstract: The incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α, TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.
  
  
  BACKGROUND
  Intravenous immunoglobulin (IVIg) treatment results in an effective response from patients with acute-phase Kawasaki disease (KD), but 16.5% of them remain nonresponsive to IVIg. To address this therapeutic challenge, we tried a new therapeutic drug, mizoribine (MZR), in a mouse model of KD, which we have established using injections of Candida albicans water-soluble fractions (CAWS).
  
  
  METHODS
  CAWS (4 mg/mouse) were injected intraperitoneally into C57BL/6N mice for 5 consecutive days. MZR or IgG was administered for 5 days. After 4 weeks, the mice were sacrificed and autopsied, the hearts were fixed in 10% neutral formalin, and plasma was taken to measure cytokines and chemokines using the Bio-Plex system.
  
  
  RESULTS
  The incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.
  
  
  CONCLUSIONS
  MZR treatment suppressed not only the incidence, range, and degree of vasculitis, but also inflammatory cytokines and chemokines in the plasma of the KD vasculitis model mice, suggesting that MZR may be useful for treatment of KD.
authors.affiliation: Inflammation Program, Dept, of Immunology, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, 260-8670, Japan. ksuzuki@faculty.chiba-u.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Takahashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Oharaseki
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Nagao
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yokouchi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Yamada
authors.forename: Noriko
authors.initials: N
authors.lastname: Nagi-Miura
authors.forename: Naohito
authors.initials: N
authors.lastname: Ohno
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Saji
authors.forename: Tomio
authors.initials: T
authors.lastname: Okazaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Suzuki