title: Markedly increased IL-18 liver expression in adult-onset Still's disease-related hepatitis.
abstract: OBJECTIVE
  First, to investigate the prevalence of liver involvement in adult-onset Still's disease (AOSD) Italian patients; secondly, to measure serum IL-18 concentration and correlate its level to other inflammatory markers and disease activity; and thirdly to characterize the expression level and the cellular source of IL-18 in the liver of a patient with AOSD with hepatitis.
  
  
  METHODS
  The clinical charts of 41 consecutive Italian AOSD patients were evaluated with special attention to liver involvement. Serum levels of IL-18 were measured in 21 patients. Finally, the case of a 33-year-old woman with hepatitis where a liver biopsy was obtained and sections stained with antibodies against IL-18 and CD68 is described in detail.
  
  
  RESULTS
  Of the 41 AOSD patients, 32 and 39% displayed increased AST level or ALT level, respectively, generally normalizing with steroid treatment, while 41% had evidence of hepatosplenomegaly. Circulating IL-18 levels were significantly higher in those with active disease compared with 85 controls. A correlation was observed between IL-18 serum level and disease activity, serum ferritin level and neutrophil count. IL-18 concentration was markedly increased in the patient with active hepatitis. Intense IL-18 expression was detected within the liver parenchyma and double staining with IL-18 and CD68 clearly showed colocalization of the cytokine with the macrophage marker.
  
  
  CONCLUSIONS
  Macrophage-derived IL-18 might play a central role in the pathogenesis of AOSD. IL-18 serum level is higher in patients with active AOSD and its local, rather than systemic, expression may be responsible for tissue damage in some target organs, such as liver.
authors.affiliation: UOC Reumatologia, Sapienza Università di Roma, Rome 00161, Italy. rob.pri@libero.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Priori
authors.forename: Francesca
authors.initials: F
authors.lastname: Barone
authors.forename: Cristiano
authors.initials: C
authors.lastname: Alessandri
authors.forename: Serena
authors.initials: S
authors.lastname: Colafrancesco
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: Costantino
authors.initials: C
authors.lastname: Pitzalis
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
authors.forename: Michele
authors.initials: M
authors.lastname: Bombardieri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000378:metabolism; D000906:Antibodies / Q000097:blood; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D006505:Hepatitis / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D020382:Interleukin-18 / Q000378:metabolism*; D007558:Italy / Q000453:epidemiology; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D012720:Severity of Illness Index; D016706:Still's Disease, Adult-Onset / Q000150:complications* / Q000378:metabolism*; D055815:Young Adult; D000097382:CD68 Molecule
chemical_list: D000410:Alanine Transaminase; D000906:Antibodies; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001219:Aspartate Aminotransferases; D015415:Biomarkers; D020382:Interleukin-18; C067980:CD68 antigen, human; D000097382:CD68 Molecule