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Attenuation of early atherosclerotic lesions by immunotolerance with β2 glycoprotein I and the immunomodulatory effectors interleukin 2 and 10 in a murine model.

Abstract：

OBJECTIVE:This study assessed the effect of cellular and humoral autoimmune response inhibition after immunization with β2-glycoprotein I (β2-GPI) and the effect of immunomodulation with interleukin (IL)-2 and IL-10 in the development of early atherosclerotic vascular lesion in a murine model. Atherosclerosis is increasingly considered a chronic inflammatory disease with pathogenic autoimmune processes. Regulatory T cells, and their cytokines, have been implicated in the inhibition of the development of atherosclerotic lesions and involved in the immunologic tolerance induction. METHODS:Eight-week-old male C57BL6 LDL-receptor deficient (LDLR(-/-)) mice were fed a cholesterol-rich (2.8%), high-saturated-fat (82%) diet for a week and divided in five groups. The groups received the following intravenous immunizations: group I (control group): one dose of 5 μg β2-GPI; group II: 5 μg β2-GPI I and 1 μg IL-2; group III: 5 μg β2-GPI and 0.75 μg of IL-10; and group IV: 5 μg β2-GPI, 1 μg IL-2, and 0.75 μg IL-10. The aortas of the mice were assessed 8 weeks after inoculation to determine the aortic lesion size and composition in all groups. RESULTS:β2-GPI immunization attenuated the early atherosclerotic lesions development compared with the control group (P = .001). Macroscopic and histologic aortic atherosclerotic lesions were significantly decreased in the IL-2 and IL-10-treated groups in β2-GPI-tolerant mice compared with the β2-GPI-tolerant group without cytokine injection (P = .001). The association of both cytokines did not provoke a major inhibition in the atherosclerosis development when compared with groups injected with the two cytokines separately. CONCLUSIONS:The immunotolerance induction against β2-GPI attenuates the development of atherosclerosis lesions in an animal model, enhanced by downregulation of the cellular and humoral autoimmune response provoked by IL-2 and IL-10.

journal_name

J Vasc Surg

journal_title

Journal of vascular surgery

authors

De Haro J,Esparza L,Bleda S,Varela C,Sanchez C,Acin F

doi

10.1016/j.jvs.2014.05.096

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

1625-31

issue

eissn

0741-5214

issn

1097-6809

pii

S0741-5214(14)01122-7

journal_volume

pub_type

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Attenuation of early atherosclerotic lesions by immunotolerance with β2 glycoprotein I and the immunomodulatory effectors interleukin 2 and 10 in a murine model.