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 adminis tered either recombinant IFN-gamma (100 U/g body weight) or phosphate buffe red saline daily for 30 days to atherosclerosis-susceptible apolipoprotein E-/- mice (16-week-old male mice, n = 11 per group) fed a normal diet. Athe rosclerotic lesion size was quantified in the ascending aorta. The number o f T lymphocytes and major histocompatibility complex (MHC) class II-positiv e cells within lesions were also quantified in this region, IFN-gamma admin istration reduced serum cholesterol concentrations by 15% (P = 0.02), For b oth groups, the majority of cholesterol was present in very low density lip oproteins, which were modestly reduced in mice receiving IFN-gamma. Despite the decrease in set-um cholesterol concentrations, IFN-gamma injections si gnificantly increased lesion size twofold compared to controls (119,980 +/- 18,536 vs. 59,396 +/- 20,017 mum(2); P = 0.038), IFN-gamma also significan tly increased the mean number of T lymphocytes (19 +/- 4 us. 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.