Interleukin-6 stimulates hepatic triglyceride secretion in rats.
Interleukin-6 (IL-6) not only regulates a variety of immune functions, but also is the most potent cytokine in inducing the hepatic acute phase proteins. We determined the effect of IL-6 on serum lipid levels and the mechanism of IL-6-induced hypertriglyceridemia in rats. Intravenous administration of IL-6 (0.1-10 micrograms/200 g BW) increased serum triglyceride levels in a dose-dependent manner. One hour after IL-6 administration, serum triglyceride levels were increased, with peak values at 2 h (2.2-fold increase). Serum cholesterol levels also increased, but the effect was delayed, first occurring at 4 h and peaking at 8 h (1.24-fold increase). IL-6 treatment increased hepatic triglyceride secretion without decreasing the clearance of triglyceride-rich lipoproteins, indicating that the hypertriglyceridemia was due to increased secretion by the liver. Furthermore, IL-6 stimulates lipolysis, and the increased delivery of FFA to the liver significantly contributed to the IL-6-induced hypertriglyceridemia. Neither alpha 1- nor beta-adrenergic receptor antagonists affected the hypertriglyceridemia induced by IL-6, whereas previous studies have shown that endotoxin-induced hypertriglyceridemia was blocked by alpha-adrenergic receptor antagonists. These results demonstrate that IL-6 induces hypertriglyceridemia by stimulating hepatic triglyceride secretion independent of endogenous catecholamines. Thus, changes in hepatic triglyceride metabolism are another acute phase response that can be induced by IL-6.
Nonogaki
K
K
Department of Medicine, University of California, San Francisco 94143, USA.
Fuller
G M
GM
Fuentes
N L
NL
Moser
A H
AH
Staprans
I
I
Grunfeld
C
C
Feingold
K R
KR
D000818:Animals; D002914:Chylomicrons / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
D002914:Chylomicrons; D003902:Detergents; D005230:Fatty Acids, Nonesterified; D015850:Interleukin-6; D011994:Recombinant Proteins; D014280:Triglycerides; D010660:Phenylisopropyladenosine; D011092:Polyethylene Glycols; D011433:Propranolol; D011224:Prazosin; C016811:tyloxapol