Immunomodulation of the inflammatory response in atherosclerosis.
OBJECTIVE
Cardiovascular disease, as manifested in the formation of atherosclerotic lesions, can be described as a chronic inflammatory autoimmune-like disease that proceeds in the context of enhanced plasma lipid levels. Modulation of the immune response may therefore form a valuable therapy in addition to standardized cholesterol and blood pressure-lowering therapies. The purpose of this review is to describe a number of recent approaches to immunomodulate atherosclerosis: immunization against mediators involved in atherosclerosis, such as cytokines and modified low-density lipoprotein; intervention in cytokine pathways; intervention in co-stimulatory pathways; activation of regulatory T cells; and modulation of natural killer T cells.


RESULTS
The most recent findings point to an important role for regulatory T cells in atherosclerotic lesion formation. The function of the regulatory T cells is modulated by chemokines and by co-stimulatory pathways, whereas the function of these cells can be strongly upregulated by anti-CD3 treatment and tolerance induction.


CONCLUSIONS
In the near future the first exponents of this approach, such as immunization and enhancement of the function of regulatory T cells, may enter the first phase of clinical trials, and may ultimately add to the current therapies in atherosclerosis.
Kuiper
Johan
J
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands. j.kuiper@lacdr.leidenuniv.nl
van Puijvelde
Gijs H M
GH
van Wanrooij
Eva J A
EJ
van Es
Thomas
T
Habets
Kim
K
Hauer
Arnaud D
AD
van den Berkel
Theo J C
TJ
D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
D016207:Cytokines