Effects of tumor necrosis factor-alpha on glucose and albumin production in primary cultures of rat hepatocytes.

Tumor necrosis factor-alpha (TNF) is known to alter significantly in vivo hepatic glucose and albumin metabolism. However, it remains unclear whether the observed effects represent direct actions of this factor or secondary responses due to the recruitment of other mediator systems. The present study was designed to investigate direct actions of TNF on glucose and albumin production in primary cultures of rat hepatocytes. Addition of TNF to the culture medium resulted in a 45% to 50% reduction in glucose production from a control level of 239 +/- 15 nmol/plate.h. This effect was reversed by addition of anti-TNF monoclonal antibody. In glycogen-depleted cells, short-term (5-hour) incubation with TNF did not affect hepatocyte albumin secretion, which was 8.13 +/- 0.29 microgram/plate.h. However, in cells exposed to insulin or in non-glycogen-depleted cells, addition of TNF resulted in a 10% to 25% reduction in albumin production. These findings indicate that TNF exerts direct inhibitory effects on hepatocyte glucose and albumin production, but the effects on the latter process are modest. A notable aspect of the findings is that the albumin effects are insulin or glucose substrate-dependent, which may have implications regarding liver function during nutritional support in critical illness.