IL-15 aggravates atherosclerotic lesion development in LDL receptor deficient mice.
BACKGROUND
Interleukin 15 (IL-15) is a pro-inflammatory cytokine involved in inflammatory diseases and IL-15 is expressed in atherosclerotic plaques.


METHODS
To establish the role of IL-15 in atherosclerosis we studied the effect of IL-15 on atherosclerosis associated cells in vitro and in vivo by neutralizing IL-15 using a DNA vaccination strategy.


RESULTS
Upon feeding a Western type diet LDLr(-/-) mice do express higher levels of IL-15 within the spleen and the number of IL-15 expressing cells among blood leukocytes and spleen cells is increased. Addition of IL-15 to macrophages induces the expression TNF-α and CCL-2. After the mice were vaccinated against IL-15, we observe a reduction in plaque size of 75% plaque. Unexpectedly, the relative number of macrophages within the plaque was 2-fold higher in IL-15 vaccinated mice than in control mice. Vaccination against IL-15 leads to an increased cytotoxicity against IL-15 overexpressing target cells, resulting in a reduction in IL-15 expressing cells and macrophages in blood and spleen and a decreased CD4/CD8 ratio.


CONCLUSIONS
Hypercholesterolemia leads to upregulation of IL-15 within spleen and blood. DNA vaccination against IL-15 does markedly reduces atherosclerotic lesion size, but does not promote lesion stability.
Division of Biopharmaceutics, LACDR, Leiden University, Leiden, The Netherlands.
Thomas
T
van Es
Gijs H M
GH
van Puijvelde
Ingrid N
IN
Michon
Eva J A
EJ
van Wanrooij
Paula
P
de Vos
Niels
N
Peterse
Theo J C
TJ
van Berkel
Johan
J
Kuiper
D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D019409:Interleukin-15 / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000633:toxicity*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D011973:Receptors, LDL / Q000172:deficiency*; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D019409:Interleukin-15; D011973:Receptors, LDL; D014409:Tumor Necrosis Factor-alpha