Macrophage-mediated modulation of hepatocyte protein synthesis. Effect of dexamethasone

G. A. Keller, M. A. West, F. B. Cerra and R. L. Simmons

We have previously reported an in vitro model demonstrating decreased hepatocyte protein synthesis following co-culture with macrophage-rich peritoneal cells (MRPC) in Sprague-Dawley rats. These observations have been proposed by us and others to represent a possible model for macrophage- or Kupffer cell-mediated modulation of hepatocyte function. Such a mechanism may play a role in the etiology of hepatic failure in sepsis. This effect is shown in this investigation to be completely blocked by dexamethasone at concentrations equal to or greater than 10(-9) M. The presence of lymphocyte-activating factor in the MRPC-conditioned medium is suppressed at the same concentration of dexamethasone. Resident MRPC were shown to secrete significant amounts of lymphocyte-activating factor activity without further in vitro activation. These results support the concept that the MRPC mediation of decreased hepatocyte protein synthesis is inflammatory in nature and possibly associated with macrophage activation.