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(American Journal of Pathology. 2000;157:1819-1824.)
© 2000 American Society for Investigative Pathology

Short Communications

Exogenous Interferon-{gamma} Enhances Atherosclerosis in Apolipoprotein E-/- Mice

Stewart C. Whitman, Punnaivanam Ravisankar, Haley Elam and Alan Daugherty

From the Gill Heart Institute, Atherosclerosis Research Group, Division of Cardiovascular Medicine, University of Kentucky, Lexington, Kentucky

A role for interferon-{gamma} (IFN-{gamma}) has been implied in the atherogenic process. To determine whether exogenously administered IFN-{gamma} exerts an effect on the development of atherosclerosis, we intraperitoneally administered either recombinant IFN-{gamma} (100 U/g body weight) or phosphate buffered saline daily for 30 days to atherosclerosis-susceptible apolipoprotein E-/- mice (16-week-old male mice, n = 11 per group) fed a normal diet. Atherosclerotic lesion size was quantified in the ascending aorta. The number of T lymphocytes and major histocompatibility complex (MHC) class II-positive cells within lesions were also quantified in this region. IFN-{gamma} administration reduced serum cholesterol concentrations by 15% (P = 0.02). For both groups, the majority of cholesterol was present in very low density lipoproteins, which were modestly reduced in mice receiving IFN-{gamma}. Despite the decrease in serum cholesterol concentrations, IFN-{gamma} injections significantly increased lesion size twofold compared to controls (119,980 ± 18,536 vs. 59,396 ± 20,017 µm2; P = 0.038). IFN-{gamma} also significantly increased the mean number of T lymphocytes (19 ± 4 vs. 7 ± 1 cells; P = 0.03) and MHC class II-positive cells (10 ± 3 vs. 3 ± 1 cells; P = 0.04) within lesions. These data lend further support to a pro-atherogenic role of IFN-{gamma}.




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