Simultaneous expression of Th1 cytokines and IL-4 conferes severe characteristics to type I autoimmune hepatitis in children.

A CHERÑAVSKY* (PRIEMR AUTOR); NATALIA PERIOLO* (PRIMER AUTOR); MARIA BARBARA DE BIASIO; NATALIA PERIOLO; JAVIER GONI; CRISTINA GALOPPO; MARıA CRISTINA CANERO-VELASCO; ALBERTO EDUARDO MUNOZ; HUGO FAINBOIM; LEONARDO FAINBOIM

HUMAN IMMUNOLOGY

ELSEVIER

Lugar: New York; Año: 2004 vol. 65 p. 683 - 691

0198-8859

To investigate the immunopathogenic mechanisms of type I autoimmune hepatitis in children, we analyzed by quantitative or semiquantitative reverse transcription-polymerase chain reaction the expression of cytokines interferon (IFN)-γ, interleukin (IL)-12p40, IL-18, IL-4, IL-10, and IL-12Rβ2. In addition, liver and peripheral blood was collected to investigate the expression of the natural killer T (NKT) cell marker Vα24. The presence of NKT cells in hepatic lesions were also identified by immunohistochemistry. The analysis was performed on liver biopsies from 25 children with type I autoimmune hepatitis. As disease controls, we included six children with hepatitis C virus?related chronic hepatitis and nine control livers. The expression of IFN-γ and IL-12p40 was not detected in controls but was clearly upregulated in pathologic biopsies. In addition, these samples showed an increased expression of IL-18 (p = 0.0003), IL-4 (p = 0.0055), and IL-12Rβ2 (p = 0.007). Western blot analysis confirmed the expression of IL-12p40 and IL-18. However, for IL-18, we detected only the immature biologically inactive polypeptide. The Vα24 transcripts were found increased in the liver (p = 0.0007) where Vα24+ cells were also localized, but decreased in peripheral blood mononuclear cells (p = 0.041). In addition to a type I immune response, NKT cells might play a substantial role in the pathogenesis of type I autoimmune hepatitis in children