Intrahepatic expression of inducible nitric oxide synthase in acute liver allograft rejection: Evidence of modulation by corticosteroids

Nitric oxide (NO) has been proposed to have an important role in the immune response. Plasma nitrate levels increase during acute rejection and decrea se after treatment with corticosteroids, but little is known about its pote ntial cellular source, We studied inducible NO synthase (iNOS) expression i n liver biopsy specimens of 12 patients with acute rejection compared with biopsy specimens from the same patients after treatment with high doses of intravenous corticosteroids. We also compared iNOS expression during acute rejection with a control group (9 patients without histological rejection). iNOS expression was assessed by immunohistochemistry. Intrahepatic iNOS ex pression was only observed in the cytoplasm of hepatocytes, which were diff usely distributed throughout hepatic lobules. iNOS expression could not be shown in portal tracts, inflammatory cells, or endothelial and sinusoidal l ining cells, In patients with acute rejection, iNOS expression was signific antly stronger than in the control group (2 +/- 0.7 v 0.6 +/- 0.7; P <.05). After treatment with corticosteroids, iNOS expression decreased significan tly (2 +/- 0.7 v 1.3 +/- 0.9; P <.05), In conclusion, the findings of the p resent study show that during acute liver rejection, hepatocytes are the ma in cellular source for NO production and treatment with corticosteroids ind uces significant downregulation of intrahepatic iNOS expression.