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 micrograms/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 micrograms rhIL-1 beta/day (1.49 +/- 0.13 versus 2.23 +/- 0.08 mmol/l, p less than 0.005; rhIL-1 beta versus saline) or 4.0 micrograms rhIL-1 beta/day (1.46 +/- 0.04 versus 2.18 +/- 0.04 mmol/l,p less than 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 micrograms rhIL-1 beta/day did not affect either cholesterol esterification or total postheparin lipolytic activity in plasma. Long-term infusion with 4.0 micrograms 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 micrograms/day induced a transient decrease of food intake and a suppression of body weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)
Hermus
A R
AR
Department of Medicine, Sint Radboud University Hospital, Nijmegen, The Netherlands.
Sweep
C G
CG
Demacker
P N
PN
van der Meer
M J
MJ
Kloppenborg
P W
PW
van der Meer
J W
JW
D000818:Animals; D001831:Body Temperature; D002784:Cholesterol / Q000097:blood*; D002788:Cholesterol Esters / Q000378:metabolism; D004435:Eating / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000032:analysis; D008074:Lipoproteins / Q000097:blood; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood*
D002788:Cholesterol Esters; D007375:Interleukin-1; D008074:Lipoproteins; D011994:Recombinant Proteins; D014280:Triglycerides; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002784:Cholesterol; D008071:Lipoprotein Lipase