The effect of interferon on the metabolism of LDLs.
Interferons have been shown to lower low density lipoprotein (LDL) cholesterol concentrations by 20-50%. To evaluate the effect of interferons on LDL metabolic behavior in individuals with normal and mildly elevated LDL cholesterol levels, autologous LDL labeled with 125I was administered to subjects at baseline and during interferon treatment. Interferon beta serine (IFN-beta serine) was administered intravenously at 4.5 x 10(6) units daily for at least 3 weeks before the start of kinetic study and continued for an additional 2 weeks. Results were analyzed by using a multicompartmental model that allows for two intravascular LDL compartments. In normal subjects, IFN-beta serine reduced LDL cholesterol and apolipoprotein (apo) B levels by 25% and 27%, respectively (p less than 0.05); LDL apo B synthesis was decreased by 59% (p less than 0.05). In hypercholesterolemic subjects, IFN-beta serine reduced LDL cholesterol levels by 38% (p less than 0.05); however, apo B concentrations and production rates were not significantly decreased. Clearance of LDL from the first intravascular apo B pool was markedly reduced in these subjects, resulting in a shift in the distribution of LDL apo B from the second to the first intravascular LDL apo B pool. We conclude that interferon's actions on LDL metabolism differ in normocholesterolemic and hypercholesterolemic subjects. In normal subjects, interferon decreased LDL cholesterol and apo B levels through a reduction in the LDL apo B production rate. However, in hypercholesterolemic subjects, interferon reduced LDL cholesterol by altering the distribution of apo B mass between LDL subspecies.
Schectman
G
G
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Kaul
S
S
Mueller
R A
RA
Borden
E C
EC
Kissebah
A H
AH
D000328:Adult; D001055:Apolipoproteins B / Q000378:metabolism; D002352:Carrier Proteins / Q000032:analysis; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL / Q000378:metabolism; D005260:Female; D006023:Glycoproteins; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D001055:Apolipoproteins B; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a