Impairment of TNF-α expression and secretion in primary rat liver cell cultures by acetaminophen treatment

Tumor necrosis factor-α (TNF-α) 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 acetaminophen in vivo on TNF-α transcript concentrations and serum TNF-α concentrations, under different experimental, or clinical conditions have yielded controversial results. We used primary rat hepatocyte and Kupffer cell cultures to test the direct action of subtoxic and toxic concentrations of acetaminophen on TNF-α expression and release. We observed a dose-dependent decrease of TNF-α mRNA in the hepatocytes, and of TNF-α release into the medium of hepatocyte cultures. The data also indicate an impairment of TNF-α release in Kupffer cell cultures after treatment with nontoxic, as well as with toxic, acetaminophen concentrations. The results suggest that inhibition of TNF-α expression and release in the liver is a consequence of acetaminophen exposure. It is at present unknown how this effect modulates the course of acetaminophen intoxication.