Role of Interferon- in Hypercholesterolemia-Induced Leukocyte–Endothelial Cell Adhesion

Background—A T-cell–mediated inflammatory response occurs in the microcirculation during acute hypercholesterolemia. The objective of this study was to define the contribution of T-lymphocyte–derived interferon(IFN) to the leukocyte–endothelial cell adhesion induced by hypercholesterolemia. Methods and Results—Intravital videomicroscopy was used to quantify the adhesion and emigration of leukocytes and oxidant stress (dihydrorhodamine [DHR] oxidation) in cremasteric venules. Wild-type (WT), IFN/ , and severe combined immunodeficiency (SCID) mice were placed on either a normal (ND) or high-cholesterol (HC) diet for 2 weeks. WT-HC mice exhibited exaggerated adhesion and emigration of leukocytes and enhanced DHR oxidation compared with WT-ND. The exaggerated adhesion responses and increased DHR oxidation were not seen in IFN/ –HC mice. SCID-HC mice also exhibited attenuated inflammatory responses compared with WT-HC. Reconstitution of either SCID-HC or IFN/ –HC mice with WT-HC splenocytes restored the inflammatory responses, whereas reconstitution of SCID-HC with IFN/ –HC splenocytes did not. The HC-induced oxidant stress was restored in IFN/ –HC mice reconstituted with WT-HC splenocytes. Conclusions—These findings implicate IFNas a cause of the inflammatory phenotype that is assumed by the microvasculature of hypercholesterolemic mice and suggest that T lymphocytes are a major source of this proinflammatory cytokine. (Circulation. 2003;107:2140-2145.)