Impairment of TNF-alpha expression and secretion in primary rat liver cellcultures by acetaminophen treatment

Tumor necrosis factor-alpha (TNF-alpha) is assumed to act as a mediator in toxic liver injury, aggravating the primary damage to the parenchymal liver cell, but also stimulating liver regeneration. Reports on the effect of ac etaminophen in vivo on TNF-alpha transcript concentrations and serum TNF-al pha concentrations, under different experimental, or clinical conditions ha ve yielded controversial results. We used primary rat hepatocyte and Kupffe r cell cultures to test the direct action of subtoxic and toxic concentrati ons of acetaminophen on TNF-alpha expression and release. We observed a dos e-dependent decrease of TNF-alpha mRNA in the hepatocytes, and of TNF-alpha release into the medium of hepatocyte cultures. The data also indicate an impairment of TNF-alpha release in Kupffer cell cultures after treatment wi th nontoxic, as well as with toxic, acetaminophen concentrations. The resul ts suggest that inhibition of TNF-alpha expression and release in the liver is a consequence of acetaminophen exposure. It is at present unknown how t his effect modulates the course of acetaminophen intoxication. (C) 1999 Els evier Science Ireland Ltd. All rights reserved.