RGD Reference Report - Elevation of serum interleukin-18 levels and activation of Kupffer cells in biliary atresia. - Rat Genome Database

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

Authors: Urushihara, N  Iwagaki, H  Yagi, T  Kohka, H  Kobashi, K  Morimoto, Y  Yoshino, T  Tanimoto, T  Kurimoto, M  Tanaka, N 
Citation: Urushihara N, etal., J Pediatr Surg. 2000 Mar;35(3):446-9.
RGD ID: 14695529
Pubmed: PMID:10726686   (View Abstract at PubMed)


BACKGROUND/PURPOSE: Interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) is a novel proinflammatory cytokine that can induce interferon gamma (IFN-gamma). 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL18Humanbiliary atresia  IEP protein:increased expression:serum:RGD 
Il18Ratbiliary atresia  ISOIL18 (Homo sapiens)protein:increased expression:serum:RGD 
Il18Mousebiliary atresia  ISOIL18 (Homo sapiens)protein:increased expression:serum:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il18  (interleukin 18)

Genes (Mus musculus)
Il18  (interleukin 18)

Genes (Homo sapiens)
IL18  (interleukin 18)


Additional Information