Depressed cytotoxic activity of hepatic nonparenchymal cells in rats with obstructive jaundice

Abstract

The nonparenchymal cells (NPC) of the liver have strong cytotoxic activity. Our hypothesis is that their activity may be imparted by obstructive jaundice and show recovery after biliary drainage. In Donryu rats, we performed either a sham operation (group C; n = 5), production of irreversible obstructive jaundice (group J; n = 5), or production of reversible obstructive jaundice for 7 days, with biliary drainage then provided for 3 days (group Ds; n = 5) or for 14 days (group Dl; n = 5). Natural killer (NK)-cell activities shown against YAC-1 lymphoma cells of hepatic NPC and peripheral blood mononuclear cells were assessed. We then measured the growth of experimental liver metastases 13 days after inoculation of a tumor cell line (AH130) into the portal vein of rats that had undergone similar biliary manipulations (group mC, group mJ, group mDs, and group mDl; n = 5 in each group). The highest number of NK activities by NPC in group J (11.5%) and group Ds (37.7%) were significantly lower than those in group C (68.8%) and group Dl (90.5%; effector/target ratios, 40:1; P < .01). NK activity of peripheral blood mononuclear cells was similar among groups. Metastatic liver tumors in group mJ (10.2% +/- 2.6%) and group mDs (5.4% +/- 1.5%) were significantly larger than in group mC (0.4% +/- 0.1%) and group mDl (0.5% +/- 0.3%; P < .02). Obstructive jaundice depressed the NK activity of hepatic NPC and enhanced the growth of liver metastases. To counter this depression, adequate biliary drainage was required. These results suggest that preoperative biliary drainage to relieve obstructive jaundice might help to prevent liver metastases after surgery for biliary tract or pancreatic tumors.