Suppression of natural killer cell activity in biliary obstruction

Prior studies regarding immune function in bile-duct ligated rats have illustrated blunted immune function. The present study measures natural killer (NK) cell activity. Rats underwent bile duct ligation (BDL) or sham celiotomy (SC) and were sacrificed at 1, 2, and 3 weeks after surgery. Ficoll-Hypaque density centrifugation was used to obtain a purified preparation of splenocytes. NK cell activity was determined by incubating varying concentrations of splenocytes with chromium-labelled YAC-1 tumor cells for 4 hours. Chromium release was measured by a gamma counter and expressed as per cent activity (compared with 100 per cent activity obtained by complete lysis with detergent). The experiments were repeated after preincubation in tissue culture flasks to remove an adherent cell population. NK cell activity was decreased at all spleen cell:target cell ratios studies at 1 week after BDL. At 2 weeks after BDL, NK cell activity was decreased at all but the lowest two concentrations; and 3 weeks after BDL, NK cell activity was decreased only at the highest concentrations used. Separation of an adherent cell fraction restored NK cell activity. This suppression in NK cell activity one week after BDL may account, in part, for the poor response of BDL animals to bacterial and immune challenge. Restoration of activity after removal of an adherent cell fraction suggests that macrophages may be at least partly responsible for this inhibition.