Effects of cytokines, bacterial endotoxin and hydrocortisone on primary hepatocyte cultures of rat and hamster.
In vivo an acute phase reaction is characterized by changes in hepatic protein metabolism and modification of liver drug enzymes (cytochrome P-450). In vitro, mediators of an acute phase reaction have been reported to have a similar effect. In the present study, the effects of bacterial endotoxin (lipopolysaccharide, LPS) and cytokines in hepatocyte cultures of rat and hamster were examined. In both species, a significant increase in secretion of specific acute phase protein was measured after 48 hr of exposure to IL-6, TNF-alpha or LPS. LPS and TNF-alpha increased the secretion of serum amyloid A (SAA) in hamster hepatocytes. LPS and IL-6 (but only in the presence of hydrocortisone) increased the secretion of alpha(2)-macroglobulin (alpha(2)M) in rat hepatocytes. An effect on the total concentration of cytochrome P-450 was not found in either species after exposure to glucocorticoids or to LPS and cytokines, although the latter compounds caused a marked increase in secretion of acute phase proteins.
Toussaint
M J
MJ
Department of Veterinary Pathology, University of Utrecht, PO Box 80158, 3508 TD, Utrecht, The Netherlands.
Niewold
T A
TA
de Wit
M M
MM