Freunds adjuvant alone is antiatherogenic in apoE-deficient mice and specific immunization against TNFα confers no additional benefit

Peter Riis Hansen, Michelle Chew, Ji Zhou, Alan Daugherty, Niels Heegaard, Per Jensen, Soren Mouritsen, Erling Falk

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


TNFα participates in the pathogenesis of atherosclerosis. The effect of immunization against TNFα on development of advanced vascular lesions in atherosclerosis-susceptible apoE-deficient mice was investigated. At 5-7 weeks of age, animals received immunization with either Freunds adjuvant and a recombinant antigenic TNFα molecule (TNF106), Freunds adjuvant alone, or no immunization. All mice received a Western-type high-fat diet for 12 weeks. Aortic sinus lesion area was determined by microscopic morphometry, the total aortic arch cholesterol content was determined by gas chromatography, and antibodies against TNFα, malondialdehyde-modified low density lipoprotein, or heat shock protein 60, were assessed by ELISAs. Immunization with TNF106 induced high-titered circulating antibodies against TNFα (n = 23), and these antibodies were not detected in mice immunized with Freunds adjuvant alone (n = 22), or in non-immunized control animals (n = 25). After 12 weeks, the atherosclerotic lesion size was significantly reduced in immunized animals, whether they had been immunized with TNF106 or Freunds adjuvant alone, and the total lesional cholesterol content was decreased in mice immunized with TNF106. There were no correlations between circulating antibody titers and plaque size, total aortic arch cholesterol content, or plasma lipid levels, respectively. Administration of Freunds adjuvant alone can thus reduce formation of mature atherosclerotic lesions in apoE-deficient mice and this response is not modified by specific immunization against TNFα.

Original languageEnglish
Pages (from-to)87-94
Number of pages8
Issue number1
StatePublished - 2001

Bibliographical note

Funding Information:
This study was supported by grants from the Danish Heart Foundation. Svend Ellermann-Eriksen, MD, Anne Mette Holm, MS, Erik Lindblad, MS, and Jan Møller, MS, are acknowledged for assistance.


  • Apolipoprotein E knockout
  • Atherosclerosis
  • Freunds adjuvant
  • Immunization
  • Immunology
  • Inflammation
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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