TUMOR-NECROSIS-FACTOR INCREASES HEPATIC CELL MASS

The effect of tumour necrosis factor (TNF) on hepatic cellularity was investigated in male Wistar rats maintained on total parenteral nutrition. Twenty-eight rats were infused with TNF (2 X 10(5) units TNF-alpha kg-1 24 h-1) or saline (controls) for 6 days. Wet and dry liver weights and nitrogen content were significantly increased by TNF (P < 0.001), indicating an increase in liver mass. A further 81 rats were infused with TNF (2 or 4 X 10(5) units kg-1 24 h-1) or saline over 1, 3 and 6 days. Total liver DNA and protein content and counts of hepatocyte mitosis were determined. Liver DNA and protein increased with dose of TNF and time (P < 0.001), suggesting that TNF increased hepatic cellularity. Histological examination demonstrated no significant inflammatory infiltrate to account for the increased cell mass. However, the number of hepatocyte mitoses increased with dose of TNF and time (P < 0.05), indicating that the increase in liver cellularity was due to increased hepatocyte cell number. TNF-induced hepatic hyperplasia appears to be an additional feature of the integrated host response to injury and infection.