CONTINUOUS INFUSION OF INTERLEUKIN-1-BETA IN RATS INDUCES A PROFOUND FALL IN PLASMA-LEVELS OF CHOLESTEROL AND TRIGLYCERIDES

During infectious diseases, striking alterations in plasma concentrations of cholesterol (hypocholesterolemia) and triglycerides (hypertriglyceridemia) may occur. It has been suggested that interleukin-1 is a mediator of these alterations. We studied the effects of continuous administration of recombinant human interleukin-1-beta (rhIL-1-beta) on plasma levels of cholesterol and triglycerides. A total of 42 rats were equipped with minipumps loaded with either rhIL-1-beta (delivery rate of 0.5, 2.0, or 4.0-mu-g/day i.p. for 1 week) or saline. After 1 day of treatment with rhIL-1-beta, plasma cholesterol levels had not changed. On day 2 a remarkable decrease of plasma cholesterol levels was observed in rats treated with 2.0-mu-g rhIL-1-beta/day (1.49+/-0.13 versus 2.23+/-0.08 mmol/l, p<0.005; rhIL-1-beta versus saline) or 4.0-mu-g rhIL-1-beta/day (1.46+/-0.04 versus 2.18+/-0.04 mmol/l,p<0.0005). This decrease persisted until the end of the experiment and occurred in all major lipoprotein fractions. Triglycerides in plasma (and in very low density lipoprotein) decreased almost concomitantly with plasma cholesterol, although to a lesser degree. Infusion of 2.0-mu-g rhIL-1-beta/day did not affect either cholesterol esterification or total postheparin lipolytic activity in plasma. Long-term infusion with 4.0-mu-g rhIL-1-beta/day induced prolonged fever, whereas at the lower doses temperatures were elevated only the first 2 days. rhIL-1-beta at a dose of 2.0 and 4.0-mu-g/day induced a transient decrease of food intake and a suppression of body weight gain. Restriction of food consumption to the level observed in the 2.0-mu-g rhIL-1-beta experiment caused only a small decrease of plasma cholesterol level and had no effects on plasma concentrations of triglycerides. Therefore, it is unlikely that the decline in triglyceride levels during rhIL-1-beta infusion was caused by a decrease in food intake. Diminished food consumption also cannot completely explain the profound decline of cholesterol levels during rhIL-1-beta administration. Whether IL-1 plays a role as a mediator of the lowering of plasma cholesterol levels during infections remains to be determined.