PMID- 10726686
OWN - NLM
STAT- MEDLINE
DCOM- 20000404
LR  - 20190710
IS  - 0022-3468 (Print)
IS  - 0022-3468 (Linking)
VI  - 35
IP  - 3
DP  - 2000 Mar
TI  - Elevation of serum interleukin-18 levels and activation of Kupffer cells in 
      biliary atresia.
PG  - 446-9
AB  - 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.
FAU - Urushihara, N
AU  - Urushihara N
AD  - Department of Surgery, Okayama University Medical School, Japan.
FAU - Iwagaki, H
AU  - Iwagaki H
FAU - Yagi, T
AU  - Yagi T
FAU - Kohka, H
AU  - Kohka H
FAU - Kobashi, K
AU  - Kobashi K
FAU - Morimoto, Y
AU  - Morimoto Y
FAU - Yoshino, T
AU  - Yoshino T
FAU - Tanimoto, T
AU  - Tanimoto T
FAU - Kurimoto, M
AU  - Kurimoto M
FAU - Tanaka, N
AU  - Tanaka N
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Pediatr Surg
JT  - Journal of pediatric surgery
JID - 0052631
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD68 antigen, human)
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Antigens, CD
MH  - Antigens, Differentiation, Myelomonocytic
MH  - Apoptosis
MH  - Biliary Atresia/blood/*etiology/immunology/surgery
MH  - Child
MH  - Child, Preschool
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Infant
MH  - Interleukin-18/*blood
MH  - Kupffer Cells/immunology/*physiology
MH  - Liver/immunology/pathology
MH  - Liver Transplantation
MH  - Portoenterostomy, Hepatic
MH  - Prognosis
EDAT- 2000/03/22 00:00
MHDA- 2000/03/22 00:01
CRDT- 2000/03/22 00:00
PHST- 2000/03/22 00:00 [pubmed]
PHST- 2000/03/22 00:01 [medline]
PHST- 2000/03/22 00:00 [entrez]
AID - S0022-3468(00)90211-2 [pii]
AID - 10.1016/s0022-3468(00)90211-2 [doi]
PST - ppublish
SO  - J Pediatr Surg. 2000 Mar;35(3):446-9. doi: 10.1016/s0022-3468(00)90211-2.