Plasma lipoprotein changes in humans induced by β-interferon

Rosenzweig, I. Bruce; Wiebe, Donald A.; Borden, Ernest C.; Storer, Barry E.; Shrago, Earl

doi:10.1016/0021-9150(87)90287-5

Cited by 34 publications

(16 citation statements)

References 13 publications

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“…2 - 5 Our results suggest that the primary mechanism for this effect was a reduction in the LDL apo B production rate. Nonsignificant reductions in the LDL FCR were also observed during this study.…”

Section: Discussionmentioning

confidence: 62%

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The effect of interferon on the metabolism of LDLs.

Schectman

Kaul

Mueller

et al. 1992

Arterioscler Thromb

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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 was administered to subjects at baseline and during interferon treatment Interferon beta^^,, (IFN-ft^.,,) was administered intravenously at 4.5 x 10' 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, TFN-fi mttIM 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-^KH,, 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. ( lesterol of 20% and 50% at the two doses studied, 4.5xlO 6 and 9.0 xlO 7 units, respectively. 5 Both doses were well tolerated.The mechanism behind the effects of interferons in reducing LDL cholesterol and apo B concentrations is unknown. Administration of both interferon gamma and alfa inhibits hepatic and lipoprotein lipase activity, enzymes necessary for the synthesis of LDL from very low density lipoprotein (VLDL).46 Inhibition of this pathway may result in decreased synthesis of LDL. On the other hand, interferons may act as important modulators of cellular protein synthesis by upregulating LDL receptors and enhancing LDL clearance. Because LDL synthetic and catabolic rates are abnormal in hypercholesterolemic subjects, the extent to which interferon affects LDL kinetic behavior may also depend on the presence or absence of normal lipoprotein metabolism. The effect of interferon on individuals with hypercholesterolemia has not been studied. The purpose of this study was to evaluate the effect of recombinant human IFN-fte,,,* on LDL composition and metabolism when administered to normal and mildly hypercholesterolemic subjects. Methods SubjectsKinetic studies were performed before and after intravenous administration of IFM-fte^ injections to 10 subjects. Six had mild hypercholesterolemia with LDL

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Section: Discussionmentioning

confidence: 62%

“…When administered for 10 days to patients with stable renal cancer, daily IFN-ft^tae injections produced dose-dependent reductions in LDL cho-lesterol of 20% and 50% at the two doses studied, 4.5xlO 6 and 9.0 xlO 7 units, respectively. 5 Both doses were well tolerated.…”

Section: The Effect Of Interferon On the Metabolism Of Ldlsmentioning

confidence: 97%

The effect of interferon on the metabolism of LDLs.

Schectman

Kaul

Mueller

et al. 1992

Arterioscler Thromb

View full text Add to dashboard Cite

show abstract

“…With beta-interferon, the same authors reported a dose-related decrease in low density lipoprotein but not high density lipoprotein, and an increase in very low density lipoprotein. 22 In the present study, interferon treatment for 8 weeks produced no significant changes in the beta-iipoprotein fractions. A transient significant decrease in high density lipoprotein cholesterol was detected in serum samples drawn at 4 weeks (data not shown).…”

Section: Mechanism Of Upoprotelnsmentioning

confidence: 67%

Suppression of aortic atherosclerosis in cholesterol-fed rabbits by purified rabbit interferon.

et al. 1990

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The effectiveness of rabbit Interferon In suppressing atherosclerosis was evaluated In rabbits fed a diet containing 1 % cholesterol. Ten male New Zealand White rabbits received Intramuscular Injections of 1 million units of Interferon twice a week, while a control group of 10 rabbits received Injections of buffer. Both groups had average serum cholesterol levels of over 2000 mg/dl during the 8-week experimental period. Interferon treatment resulted In no significant hypolipidemlc effect or changes In llpoproteln composition. Atherosclerotic lesions In aortas were quantified both macroscopically and microscopically. Interferon treatment decreased the grossly visible lesion area significantly from 25±4% to 8 ± 1 % (mean±SEM, p<0.005) compared to the untreated group. Microscopic analysis of serial cross-sections of aortic segments revealed significant (p<0.01) reductions In both lesion size and frequency in the Interferon-treated group. Electron microscopy also showed that Interferon treatment reduced the pathological effects of cholesterol feeding. Tissue analysis showed that total aortic cholesterol was reduced by 28% by Interferon treatment, while the aortic phosphollpid concentration was Increased by 25%. The possibility exists that the interferon preparation used contained other biological response modifiers and that the observed effects may be totally unrelated with Interferon. These results suggest that the mechanism of atherosclerosis suppression In these cholesterol-fed rabbits Is not related to the lowering of serum cholesterol but may be associated with Inhibition of lesion Initiation. A therosclerotic lesions develop as the result of the interplay between the multiple risk factors associated with Increased incidence of atherosclerosis, the cells of the arterial wall, and the circulating blood cells. 1 Increased understanding of these interactions is critical to developing new approaches to prevention and therapy.Since the discovery of interferon as an antiviral agent in 1957, interest has grown in its nonantiviral activities, 2 particularly in its use in cancer therapy. 3 Interferons exhibit a wide range of effects, each depending on the type of interferon and the nature and state of differentiation of the target cell. Interferons are involved in the inhibition of cell growth and proliferation, regulation of the expression of specific genes, modulation of cell differentiation, and activation of certain cell types in the immune system, for example, macrophages and natural killer cells. 4 The Interferon inducers, polyinoslnic-polycytidylic acid and 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (U-54,461), have been shown to suppress atherosclerosis in rabbits. 5 It is important to establish whether the Received October 28,1988; revision accepted October 20,1989. anti-atherogenic effect is a direct effect of these drugs or is mediated by interferon. The purpose of the present study was to evaluate the anti-atherogenic effectiveness of the administration of purified rabbit interferon in the cholesterol-fe...

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“…LPS, TNF, IL-2, IFN-␤, granulocyte-macrophage colony-stimulating factor, and macrophage colony-stimulating factor decrease serum cholesterol, whereas IL-1 has no effect (24,25,36,42,(93)(94)(95)(96)(97). The decrease in cholesterol is accompanied by a reduction in serum apoB levels.…”

Section: Cholesterol Metabolismmentioning

confidence: 95%