Drug influences on rat hepatic macrophage enzyme production and release in vitro

Drug influences on hepatic macrophage enzyme release have been investigated using a rat model of macrophage recruitment and activation. N-acetyl-glucosaminidase (NAG), a lysosomal enzyme, and plasminogen activator (PA), a cytosolic enzyme, have been measured in both cell lysates and supernatants after 24 h in culture. 6-mercaptopurine (6-MP) and azathioprine significantly decreased (P less than 0.03) the enhanced production of NAG by recruited macrophages following stimulation in vitro (total NAG activity, nmol substrate hydrolysed/microgram cell protein; recruited macrophages exposed to endotoxin, no drug exposure 0.63 +/- 0.08, azathioprine 0.44 +/- 0.08, 6MP 0.36 +/- 0.06). Prednisolone, azathioprine and 6MP significantly reduced (P less than 0.05) the supernatant release of PA in response to endotoxin exposure in vitro by both cell types (supernatant PA values after 24 h in culture, recruited macrophages exposed to endotoxin, no drug 26.0 +/- 2.9 units, prednisolone 18.5 +/- 1.7 units, levamisole 27.3 +/- 4.7 units, azathioprine 18.1 +/- 2.3 units, 6MP 17.3 +/- 1.5 units). The results from this study indicate that certain drugs used in human liver disease are able to modify the secretory activity of rat hepatic macrophages.