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Markedly increased IL-18 liver expression in adult-onset Still's disease-related hepatitis

2010; Oxford University Press; Volume: 50; Issue: 4 Linguagem: Inglês

10.1093/rheumatology/keq397

1462-0332

Roberta Priori, Francesca Barone, Cristiano Alessandri, Serena Colafrancesco, Iain B. McInnes, Costantino Pitzalis, Guido Valesini, Stefano Bombardieri,

Adolescent and Pediatric Healthcare

Objectives. 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. Conclusion. 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.