Increased Immune Tolerance for LDL Lowers Atherosclerosis Risk

Immune system dendritic cells that had been exposed to a combination of apolipoprotein B100 (the major protein component of low-density lipoproteins or LDL) and interleukin-10 reduced inflammation and the degree of arterial blockage in a population of hypercholesterolemic mice.

Investigators at the Karolinska Institutet (Stockholm, Sweden) conditioned laboratory cultures of mouse dendritic cells to be immunotolerant towards apolipoprotein B100 by exposing them to a combination of this apolipoprotein and the immunomodulator interleukin-10. The conditioned dendritic cells were then administered to a population of hypercholesterolemic mice that lacked LDL receptors, experienced chronic vascular inflammation, and developed severe atherosclerotic lesions and plaques.

Results published in the February 28, 2011, online edition of the journal Circulation revealed that dendritic cells treated with apolipoprotein B100 and interleukin-10 reduced proliferation of effector T cells, inhibited production of interferon-gamma, and increased de novo generation of regulatory T cells in vitro. Treatment of hypercholesterolemic mice with apolipoprotein B100-pulsed tolerogenic dendritic cells led to a significant (70%) reduction of atherosclerotic lesions in the aorta, with decreased CD4+ T-cell infiltration, and signs of reduced systemic inflammation.

"Treatments of atherosclerosis have traditionally targeted blood lipids, but a large proportion of treated patients still suffer life-threatening infarctions and stroke,” said Dr. Göran K. Hansson, professor of molecular medicine at the Karolinska Institutet. "We are now looking at the possibility of getting to the root of the problem and re-set, so to speak, the immune system's reaction to LDL, since it often has devastating consequences.”


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