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.
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.
Authors: Giacomo Germani; Kryssia Rodriguez-Castro; Francesco Paolo Russo; Marco Senzolo; Alberto Zanetto; Alberto Ferrarese; Patrizia Burra Journal: World J Gastroenterol Date: 2015-01-28 Impact factor: 5.742