The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice.
Accumulation of T cells and macrophages in atherosclerotic plaques and the formation of antibodies directed against plaque proteins suggests that adaptive immunity contributes to the development of atherosclerosis. The contribution of Th1 and Th2 helper cell subsets to atherogenesis was studied in a murine model by interbreeding apolipoprotein E-deficient (apoE(-/-)) mice with mice deficient in key cytokines that drive either Th1 responses [interleukin (IL)-12] or Th2 responses (IL-4). Compared to apoE(-/-) mice, apoE(-/-)/IL-12(-/-) mice had a 52% reduction in plaque area in the aortic root at 30 weeks of age (P < 0.001). ApoE(-/-)/IL-4(-/-) mice had a 27% reduction in plaque area compared to apoE(-/-) mice (P < 0.05) at 30 weeks of age, but their plaques were significantly larger than in apoE(-/-)/IL-12(-/-) mice at this stage (P < 0.05). By 45 weeks of age, there were no significant differences in lesion sizes in the aortic root between the strains, however apoE(-/-)/IL-4(-/-) mice showed a 58% and 64% decrease in disease in their aortic arch compared to apoE(-/-) (P < 0.05) and apoE(-/-)/IL-12(-/-) (P < 0.05) mice, respectively, and a 78% decrease in thoracic lesions compared to apoE(-/-)/IL-12(-/-) (P < 0.05). This suggests that both Th1 and Th2 cytokines play roles throughout the development of atherosclerosis in various vascular sites in apoE(-/-) mice.
Davenport
Piers
P
Centre for Inflammatory Diseases, Department of Medicine, Monash University, Monash Medical Centre Level 5 Block E, 246 Clayton Road, Clayton, Victoria, Australia 3168. piers.davenport@med.monash.edu.au
Tipping
Peter G
PG
D000818:Animals; D000917:Antibody Formation; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D018450:Disease Progression; D018664:Interleukin-12 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000276:immunology; D018655:Lymphocyte Count; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D001057:Apolipoproteins E; D017252:CD3 Complex; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D018664:Interleukin-12; D015847:Interleukin-4; D002784:Cholesterol