Simultaneous expression of Th1 cytokines and IL-4 might explain the more severe characteristics of type I autoimmune hepatitis in children

A.CHERÑAVSKY ; N.PALADINO ; A.E.RUBIO ; M.B.DE BIASIO ; M.CUARTEROLO ; J.GOÑI ; C.GALOPPO ; M.C.CAÑERO-VELASCO ; A.E. MUÑOZ ; H.FAINBOIM ; FAINBOIM, L

HUMAN IMMUNOLOGY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; 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)-
, interleukin (IL)-12p40, IL- 18, IL-4, IL-10, and IL-12R2. In addition, liver and peripheral blood was collected to investigate the expression of the natural killer T (NKT) cell marker V24. 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-
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-12R2 (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 V24 transcripts were found increased in the liver (p  0.0007) where V24 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.