Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice

• Published in: Molecular medicine (Cambridge, Mass.) Mass.), 2003-01, Vol.9 (1-2), p.10-17
• Main Authors: Caligiuri, Giuseppina, Rudling, Mats, Ollivier, Véronique, Jacob, Marie-Paule, Michel, Jean-Baptiste, Hansson, Göran K, Nicoletti, Antonino
• Format: Article
• Language: English
• Subjects: Animals; Apolipoproteins E - deficiency; Apolipoproteins E - physiology; Arteriosclerosis - etiology; Arteriosclerosis - genetics; Arteriosclerosis - metabolism; Blood Coagulation - physiology; Crosses, Genetic; Diet, Atherogenic; Interleukin-10 - deficiency; Interleukin-10 - physiology; Lipoproteins, LDL - metabolism; Lipoproteins, VLDL - metabolism; Matrix Metalloproteinases - metabolism; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Receptors, LDL - metabolism; Th1 Cells - immunology; Th2 Cells - immunology; Thrombosis - etiology; Thrombosis - genetics; Thrombosis - metabolism
• ISSN: 1076-1551; 1528-3658
• DOI: 10.1007/bf03402102

Interleukin (IL)-10 is an anti-inflammatory cytokine that may play a protective role in atherosclerosis. The aim of this study was to assess the effect of IL-10 deficiency in the apolipoprotein E knockout mouse. Apolipoprotein E deficient (E-/-) and IL-10 deficient (-/-) mice were crossed to generate E-/- x IL-10-/- double knockout mice. By 16 wk, cholesterol and triglycerides were similar in double and single knockouts but the lack of IL-10 led to increased low-density lipoprotein cholesterol whereas very-low-density lipoprotein was reduced. In parallel, T-helper 1 responses and lesion size were dramatically increased in double knockout compared with E-/- controls. At 48 wk, matrix metalloproteinases and tissue factor activities were increased in lesions of double-knockout mice. Furthermore, markers of systemic coagulation were increased, and vascular thrombosis in response to i.v. thrombin occurred more frequently in E-/- x IL-10-/- than in E-/- mice. Our findings suggest that IL-10 deficiency plays a deleterious role in atherosclerosis. The early phase of lesion development was increased, and the proteolytic and procoagulant activity was elevated in advanced lesions. These data show that IL-10 may reduce atherogenesis and improve the stability of plaques.