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 I-125 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 < 0.05); LDL apo B synthesis was decreased by 59% (p < 0.05). In hypercholesterolemic subjects, IFN-beta(serine) reduced LDL cholesterol levels by 38% (p < 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.