IL-15 aggravates atherosclerotic lesion development in LDL receptor deficient mice

• Published in: Vaccine 2011-01, Vol.29 (5), p.976-983
• Main Authors: van Es, Thomas, van Puijvelde, Gijs H.M, Michon, Ingrid N, van Wanrooij, Eva J.A, de Vos, Paula, Peterse, Niels, van Berkel, Theo J.C, Kuiper, Johan
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Applied microbiology; Atherosclerosis; Atherosclerosis - immunology; Atherosclerosis - pathology; Biological and medical sciences; Blood; Cardiovascular disease; Cell growth; Chemokine CCL2 - biosynthesis; Cloning; Cytotoxicity; Deoxyribonucleic acid; DNA; Fundamental and applied biological sciences. Psychology; Immune system; Inflammation; Interleukin-15; Interleukin-15 - antagonists & inhibitors; Interleukin-15 - immunology; Interleukin-15 - toxicity; Lesions; Leukocytes - immunology; Lymphocytes; Male; Mice; Microbiology; Mouse model; Receptors, LDL - deficiency; Spleen - immunology; T cell receptors; Tumor Necrosis Factor-alpha - biosynthesis; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Veins & arteries
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.11.037

Abstract 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. Conclusion 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.