DEPRESSION OF CYTOTOXICITY OF NONPARENCHYMAL CELLS IN THE LIVER AFTERSURGERY

Background. The nonparenchymal cells (NPCs) of the liver have a strong cytotoxic activity. Our hypothesis is that their activity, which prev ents metastases to the liver, may be impaired after operation. Methods . First, Sprague-Dawley rats underwent either a sham operation consist ing of only a laparotomy (group L, n = 10), a laparotomy and resection of a portion of the small intestine (group R, n = 10) or no operation (group C, n = 10). After 2 days liver NPCs were isolated and divided into two fractions, large and small NPCs. The cytotoxicity of the live r NPCs and of the circulating blood mononuclear cells (BMC) was assess ed. Second, we measured the growth of tumor metastases 14 days after t he inoculation of a cell line (MRMT-1) into the portal vein of rats un dergoing similar surgical stress (group R(m), n = 10 and group L(m), n = 10). Results. The natural killer cell activity (anti-YAC-1) of larg e NPCs was 38% in group R, which was significantly less (p < 0.002) th an that in groups L (72%) and C (83%). Small NPCs showed reduced natur al killer activity in groups R and L (26% and 35%, respectively) compa red with that in group C (70%) (p < 0.02). The natural killer cell act ivity of BMCs was similar in each group, and the lymphokine-activated killer cell activity (by anti-EL4) did not change in either the NPCs o r BMCs. In the second experiment the area of the tumors occupied in th e liver in the group R(m), rats was significantly greater compared wit h that in the group L, rats (p < 0.01). Conclusions. Surgical stress d epressed the cytotoxic activity of liver NPCs and enhanced the growth of metastatic liver tumors. This suggests the possibility that periope rative immunotherapy might be clinically useful in the future to preve nt liver metastases after gastrointestinal surgery.