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Increased expression of interleukin-4 during liver allograft rejection
1Laboratoire d'Immunologie et de Biologie Cellulaire, Faculté de Médecine Cochin-Port-Royal, Université Paris V, France.
Background/Aims:
To investigate the respective roles of interleukin-2 (IL-2) and IL-4 during rejection, we evaluated the expression of IL-2, IL-2 receptor and IL-4 in human liver allografts.
Methods:
Immunohistochemistry and RT-PCR were performed in liver biopsies. To determine the effects of immunosuppression and cholestasis in IL-4 production, in vitro experiments were also designed.
Results:
IL-2 protein and its mRNA were absent in the liver, with minimal expression of IL-2 receptor, during rejection. In contrast, IL-4 protein and its mRNA were highly expressed during acute and chronic rejection, whereas this expression was absent in stable liver transplant recipients. In vitro, cyclosporine potently inhibited IL-2 and IL-2 receptor expression of activated mononuclear blood cells, but poorly inhibited IL-4 expression. Chenodeoxycholic acid decreased IL-2 and IL-2 receptor expression, but increased IL-4 expression.
Conclusions:
During liver allograft rejection, IL-2 pathway is down-regulated, while IL-4 expression is increased by cholestasis and poorly inhibited by cyclosporine. These data suggest that IL-4 is involved in the mechanisms of liver allograft rejection in patients treated with cyclosporine.