Hepatic
fibrosis is a common outcome of chronic
liver diseases. In
schistosomiasis, chronic parasite egg-induced
granuloma formation can lead to
fibrosis, which is immunologically characterized by the dominant Th2 response. Recently, it has been shown that gene therapy is an attractive approach for the treatment of hepatic
fibrosis. To investigate the antifibrotic effects of
IL-18 gene transfer, a normal murine liver cell line BNL.CL2 was transfected with recombinant adenovirus encoding mouse
IL-18, and then intrasplenically transplanted into mice infected with Schistosoma japonicum (S. japonicum). Our data show that
IL-18 gene-modified hepatocytes intrasplenically transplanted into mice can effectively express
IL-18 in the liver and in peripheral blood. Intrasplenic
transplantation of
IL-18 gene-modified hepatocytes into S. japonicum-infected mice could result in a significantly increased IFN-gamma and
IL-2 but decreased
IL-4 and
IL-10 concentration both in the liver and in the serum, suggesting that the dominant Th2 response in mice with
schistosomiasis could be reversed by this intervention. Consistent with the changes in Th1 and Th2
cytokine production, mice intrasplenically transplanted with
IL-18 gene-modified hepatocytes developed much less hepatic
fibrosis at 20 weeks after
infection, which was evaluated by liver content of
hydroxyproline,
collagens, and hepatic
mRNA expression of procollagens. These data indicate that intrasplenic
transplantation of
IL-18 gene-modified hepatocytes can be a candidate for therapeutic intervention in hepatic
fibrosis through induction of a dominant Th1 response.