Cocultures between primary parenchymal and nonparenchymal liver cells improve the reliability of results from in vitro toxicity testing.

Cocultures between primary parenchymal and nonparenchymal liver cells impro ve the reliability of results from in vitro toxicity testing. Conventional homotypic hepatocyte cultures do not include the possible cont ribution of nonparenchymal liver cells, particularly Kupffer cells, to the pharmacological and toxicological consequences after exposure to xenobiotic s. Therefore the exchange of soluble factors between liver cells was invest igated in cocultures between primary, freshly isolated cultured rat hepatoc ytes and Kupffer cells. Cocultures were exposed to endotoxins in combinatio n with phenobarbital, 3-methylcholanthrene or lead A strong but selective d own-regulation of xenobiotic induced cytochrome P450 isoforms was detectabl e, mediated exclusively by TNF alpha released from the Kupffer cells. Pb sy nergistically increased this endotoxin induced TNF alpha-release. The resul ts indicate that cocultures improve the reliability of data obtained from o rgan specific cell cultures and that they simulate much closer the situatio n in the intact liver.