title: Effects of TNF, IL-1, and the combination of both cytokines on cholesterol metabolism in Syrian hamsters.
abstract: 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.
authors.affiliation: Department of Medicine, University of California San Francisco UCSF.
authors.forename: I
authors.initials: I
authors.lastname: Hardardóttir
authors.forename: A H
authors.initials: AH
authors.lastname: Moser
authors.forename: R
authors.initials: R
authors.lastname: Memon
authors.forename: C
authors.initials: C
authors.lastname: Grünfeld
authors.forename: K R
authors.initials: KR
authors.lastname: Feingold
mesh_terms: 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*
chemical_list: 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