Low-dose interferon-α accelerates atherosclerosis in an LDL receptor-deficient mouse model

Abstract Background : Solid evidence suggests that atheroscleosis is associated with immune reactions. Most of the activated T cells in the plaque are T helper 1 subtype (Th1), which secrete interferon-γ (IFN-γ), now generally accepted as a proatherogenic cytokine. Interferon-α (IFN-α) has been found to inhibit the secretion of IL-12 and IFN-γ and to increase IL-10 production. It may, therefore, be atheroprotective. The aim of the present study was to clarify the effect of IFN-α on atherogenesis in a transgenic mouse model of atherosclerosis. Methods : 8-week-old low-density lipoprotein (LDL) receptor-deficient mice were allocated randomly into treatment and control groups ( n =13 each). The treatment group received 1000 units of IFN-α i.p. every other day for 5 weeks and the control mice received 0.9% NaCl. The mice were fed a Western diet. Results : The IFN-α-treated and the control mice showed a similar weight gain (mean 3.9±1.0 g vs. 3.4±1.8 g, respectively). Treatment with IFN-α significantly increased the plasma cholesterol levels in both treated and untreated mice (mean 31.03±5.53 mmol/l vs. 24.91±6.03 mmol/l, respectively; p p 2 vs. 37,272±15,469 μm 2 , respectively; p Conclusion : The putative atheroprotective effect of IFN-α by the decrease in IL-10 and IFN-γ is abolished by hyperlipidemia. Therefore, the net effect of IFN-α in this murine model is the exacerbation of atherosclerosis.