Exogenous interferon-gamma enhances atherosclerosis in apolipoprotein E-/- mice.
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 micrometer(2); 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.
Whitman
S C
SC
Gill Heart Institute, Atherosclerosis Research Group, Division of Cardiovascular Medicine, University of Kentucky, Lexington, Kentucky, USA.
Ravisankar
P
P
Elam
H
H
Daugherty
A
A
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D002784:Cholesterol / Q000097:blood; D004198:Disease Susceptibility; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins; D012016:Reference Values; D012850:Sinus of Valsalva / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology
D001057:Apolipoproteins E; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D007371:Interferon-gamma; D002784:Cholesterol