Chronic intraperitoneal infusion of low doses of tumor necrosis factor alpha in rats induces a reduction in plasma triglyceride levels.
Single and repeated bolus injections of tumor necrosis factor alpha (TNF) in laboratory animals have been reported to result in hypertriglyceridaemia, suggesting that TNF is a mediator of hypertriglyceridaemia occurring during infection. However, as during infection production of TNF is probably chronically elevated, we determined the effects of continuous infusion of low doses of TNF on plasma levels of triglycerides and cholesterol. Male rats, bearing a venous catheter to allow repeated blood sampling, were intraperitoneally equipped with osmotic minipumps which continuously delivered TNF or saline for 7 days. Infusion of rats with doses of TNF as low as 4.0 and 8.0 micrograms/24 h resulted in significant decreases in plasma levels of triglycerides as compared with those after saline infusion. Although plasma triglyceride concentrations were persistently lower in TNF than in saline animals throughout the study period, the differences were most prominent during the first days and reached statistical significance at day 1, 3, 4 and 5 and of the 4.0 micrograms experiment and on day 1, 2 and 3 of the 8.0 micrograms experiment. This suppression of plasma triglyceride concentrations was not accompanied by changes in plasma cholesterol levels. No effects of chronic TNF treatment on food intake, body weight change and rectal temperature of the animals were observed. These findings indicate that chronic infusion of low doses of TNF induces hypotriglyceridaemia in rats. The role of TNF as a factor in mediating hypertriglyceridaemia during infectious diseases needs to be reconsidered.