Effects of TNF, IL-1, and the combination of both cytokines on cholesterol metabolism in Syrian hamsters.
Infection and inflammation are associated with alterations in lipid metabolism that may be mediated by cytokines such as TNF and IL-1. This study determined the effects of TNF and IL-1 on certain aspects of cholesterol metabolism. TNF or IL-1 administration to Syrian hamsters increased serum cholesterol levels by 17 and 21%, respectively, and decreased HDL cholesterol levels by 20 and 15%, respectively. TNF + IL-1 increased serum cholesterol levels by 58% and decreased HDL cholesterol levels by 58%. TNF or IL-1 increased hepatic HMG CoA reductase mRNA levels by 3.5- and 3-fold, respectively. TNF + IL-1 increased HMG CoA reductase mRNA levels by 7-fold. IL-1 increased hepatic LDL receptor mRNA levels by 2-fold while TNF and a combination of TNF + IL-1 had minimal effects. TNF or IL-1 did not affect hepatic apo E or apo A-I mRNA levels while a combination of TNF + IL-1 decreased both mRNA levels by 50%. Our results demonstrate that TNF and IL-1 similarly affect the parameters of cholesterol metabolism studied. Furthermore, the combination of TNF + IL-1 was, in most cases, more effective than either cytokine alone, and reproduced many of the effects of LPS.
Hardardóttir
I
I
Department of Medicine, University of California San Francisco UCSF.
Moser
A H
AH
Memon
R
R
Grünfeld
C
C
Feingold
K R
KR
D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis; D001057:Apolipoproteins E / Q000096:biosynthesis; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D006224:Cricetinae; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases