title: 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.
authors.affiliation: Angiology and Vascular Surgery Department, Getafe University Hospital, Getafe, Madrid, Spain. Electronic address: deharojoaquin@yahoo.es.
authors.forename: Joaquin
authors.initials: J
authors.lastname: De Haro
authors.affiliation: Angiology and Vascular Surgery Department, Getafe University Hospital, Getafe, Madrid, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Esparza
authors.affiliation: Angiology and Vascular Surgery Department, Getafe University Hospital, Getafe, Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bleda
authors.affiliation: Angiology and Vascular Surgery Department, Getafe University Hospital, Getafe, Madrid, Spain.
authors.forename: Cesar
authors.initials: C
authors.lastname: Varela
authors.affiliation: Biomedical Research Centre, Getafe University Hospital, Getafe, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Sanchez
authors.affiliation: Angiology and Vascular Surgery Department, Getafe University Hospital, Getafe, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Acin
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology*; D007111:Immunity, Cellular; D056747:Immunomodulation / Q000187:drug effects* / Q000502:physiology; D016753:Interleukin-10 / Q000494:pharmacology* / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053482:beta 2-Glycoprotein I / Q000502:physiology*
chemical_list: D007376:Interleukin-2; D053482:beta 2-Glycoprotein I; D016753:Interleukin-10