Differential effects of interleukin-1 receptor antagonist and tumor necrosis factor binding protein on fatty-streak formation in apolipoprotein E-deficient mice

Circulation. 1998 Jan 27;97(3):242-4. doi: 10.1161/01.cir.97.3.242.

Abstract

Background: The cytokines interleukin 1 (IL-1) and tumor necrosis factor (TNF) are secreted by the different cell populations of the vascular wall and have been suggested to promote atherosclerosis.

Methods and results: Their respective roles in fatty-streak formation in apolipoprotein E-deficient mice were investigated by use of IL-1 receptor antagonist and TNF binding protein. Estradiol-17beta was used as a positive control. Blocking TNF seemed to be active in female animals but not in males. IL-1 receptor antagonist was as effective as or more effective than estradiol in both sexes.

Conclusions: IL-1 plays a crucial role in the initial step of the atherosclerotic process in this animal model, and blocking the activity of this cytokine should be considered as a therapeutic possibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency*
  • Arteriosclerosis / etiology*
  • Arteriosclerosis / pathology
  • Carrier Proteins / administration & dosage
  • Carrier Proteins / pharmacology
  • Carrier Proteins / physiology*
  • Estradiol / pharmacology
  • Female
  • Interleukin 1 Receptor Antagonist Protein
  • Lipid Metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Tumor Necrosis Factor*
  • Receptors, Tumor Necrosis Factor, Type I
  • Sialoglycoproteins / administration & dosage
  • Sialoglycoproteins / pharmacology
  • Sialoglycoproteins / physiology*
  • Tumor Necrosis Factor Decoy Receptors

Substances

  • Apolipoproteins E
  • Carrier Proteins
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Sialoglycoproteins
  • Tumor Necrosis Factor Decoy Receptors
  • recombinant human tumor necrosis factor-binding protein-1
  • Estradiol