Interleukin-18 predicts atherosclerosis progression in SIV-infected and uninfected rhesus monkeys (Macaca mulatta) on a high-fat/high-cholesterol diet.
Interleukin (IL)-18 levels have been identified as important predictors of cardiovascular mortality and are often elevated in human immunodeficiency virus (HIV)-infected individuals. To investigate a possible function for IL-18 in atherogenesis in the context of early HIV infection, we used the simian immunodeficiency model of HIV infection. Acutely simian immunodeficiency virus-infected and uninfected rhesus monkeys (Macaca mulatta) on an atherogenic diet were evaluated prospectively for atherosclerotic lesion development relative to a panel of plasma markers including IL-18, IL-8, IL-1beta, IL-6, C-reactive protein, soluble vascular cell adhesion molecule-1, soluble E-selectin, and soluble intercellular adhesion molecule-1. Although no significant differences in lesion development were identified between groups after 35 days of infection, levels of plasma IL-18 measured 1 month before virus inoculation correlated significantly with atherosclerotic plaque cross-sectional area at the carotid bifurcation (P<0.001, R=0.946), common iliac bifurcation (P<0.01, R=0.789), and cranial abdominal aorta (P<0.01, R=0.747), as well as with extent of CD3+ and CD68+ cellular infiltration in vascular lesions (both P<0.001, R>or=0.835) in both groups. Atherosclerotic plaque area at the carotid and common iliac bifurcations also showed a weaker inverse correlation with baseline IL-8 levels, as did CD68+ signal area. Results implicate a strong role for IL-18 in early atherosclerosis progression and raise the possibility that the chronically elevated IL-18 levels seen in later stages of HIV infection may contribute significantly to accelerated atherogenesis in this population.
Yearley
Jennifer H
JH
Harvard Medical School, New England Primate Research Center, Southborough, MA 01772-9102, USA.
Xia
Dongling
D
Pearson
Christine B
CB
Carville
Angela
A
Shannon
Richard P
RP
Mansfield
Keith G
KG
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood* / Q000473:pathology / Q000821:virology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004041:Dietary Fats / Q000008:administration & dosage*; D019040:E-Selectin / Q000097:blood; D007083:Iliac Artery / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood*; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D019040:E-Selectin; D020382:Interleukin-18; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein