Elevation of serum interleukin-18 levels and activation of Kupffer cells in biliary atresia

Naoto Urushihara, Hiromi Iwagaki, Takahito Yagi, Hideo Kohka, Kenta Kobashi, Yoshinori Morimoto, Tadashi Yoshino, Tadao Tanimoto, Masashi Kurimoto, Noriaki Tanaka

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)


Background/Purpose: Interleukin-18 (IL-18)/interferon-γ-inducing factor (IGIF) is a novel proinflammatory cytokine that can induce interferon gamma (IFN-γ). In addition, IL-18 enhances intracellular adhesion molecule- 1 (ICAM-1) expression as well as Fas ligand (FasL) expression, and induces apoptosis in hepatic injury. The aim of this study was to clarify the potential role of IL-18 in the pathogenesis of the progressive inflammation and fibrosis in biliary atresia (BA). Methods: Six children with BA before hepatic portoenterostomy (HPE), 13 with BA including 7 without jaundice and 6 with persistent jaundice after HPE, and 16 healthy controls were examined. Blood samples were obtained preoperatively from 6 patients, after HPE from 13, and after liver transplantation from 4. The IL-18 level was determined by an enzyme-linked immunosorbent assay (ELISA). Immunohistochemically, liver specimens from BA patients were studied using a monoclonal antibody to macrophage-associated antigen (CD68). Results: IL-18 levels were elevated in the patients before HPE compared with those of the controls (349 ± 54 pg/mL v 138 ± 13 pg/mL, P < .0001). After HPE, extremely high concentrations of IL-18 were observed in patients with persistent jaundice (532 ± 95 pg/mL, P < .0001), and the IL-18 levels were significantly high even in the patients without jaundice (249 ± 29 pg/mL, P < 0.005). The high IL-18 level lasted for a long time even in the patients without jaundice after HPE. In contrast, the IL-18 levels immediately decreased after liver transplantation. Immunohistochemically, the number of CD68-positive Kupffer cells was significantly higher, and the size was larger in the livers of the patients than in the controls. The proliferation of CD68-positive cells was much more conspicuous in the liver specimens obtained during liver transplantation than in those at the time of HPE. Conclusions: Our findings showed elevation of serum IL-18 levels and activation of Kupffer cells in BA. IL-18 released from activated Kupffer cells might play an important role in the pathophysiology of the progressive inflammation and fibrosis in BA. Furthermore, IL-18 level may be related to the prognosis in patients with BA. Copyright (C) 2000 by W.B. Saunders Company.

Original languageEnglish
Pages (from-to)446-449
Number of pages4
JournalJournal of Pediatric Surgery
Issue number3
Publication statusPublished - Mar 2000


  • Biliary atresia
  • Cytokine
  • Interferon-gamma-inducing factor
  • Interleukin-18
  • Kupffer cell

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health


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