IFN-gamma potentiates atherosclerosis in ApoE knock-out mice.

Abstract

The early colocalization of T cells and the potent immunostimulatory cytokine IFN-␥ to atherosclerotic lesions suggest that the immune system contributes to atherogenesis. Since mice with a targeted disruption of the apoE gene (apoE 0 mice) develop profound atherosclerosis, we examined the role of IFN-␥ in this process. First, the presence of CD4 ϩ and CD8 ϩ cells, which secrete lesional IFN-␥ , was documented in apoE 0 atheromata. Then, the apoE 0 mice were crossed with IFN-␥ receptor (IFN ␥ R) 0 mice to generate apoE 0/IFN ␥ R 0 mice. Compared to the apoE 0 mice, the compound knock-out mice exhibited a substantial reduction in atherosclerotic lesion size, a 60% reduction in lesion lipid accumulation, a decrease in lesion cellularity, but a marked increase in lesion collagen content. Evaluation of the plasma lipoproteins showed that the compound knockout mice had a marked increase in potentially atheroprotective phospholipid/apoA-IV rich particles as well. This correlated with an induction of hepatic apoA-IV transcripts. These observations suggest that IFN-␥ promotes and modifies atherosclerosis through both local effects in the arterial wall as well as a systemic effect on plasma lipoproteins. Therefore, therapeutic inhibition of IFN-␥ signaling may lead to the formation of more lipid-poor and stable atheromata. ( J. Clin. Invest. 1997. 99:2752-2761.)

IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis

“…Th1 adaptive responses, and Th1 cytokines in particular have been shown to play a key role in promoting atherogenesis (17,(35)(36)(37). In contrast, we now demonstrate that immunization with MDA-LDL directly triggers an antigen-specific Th2 response that is associated with an atheroprotective effect.…”

Periodontal treatment influences risk markers for atherosclerosis in patients with severe periodontitis

“…IFN-␥ plays a role in the development of atherosclerosis, both as a consequence of its effects on plaque progression/stability [25,26] and via its negative impact on blood lipid trafficking (for review see Leon and Zuckerman [27]). In our present study, treatment reduced the plasma concentration of IFN-␥ by more than 90%.…”

T Helper–Cell Phenotype Regulates Atherosclerosis in Mice Under Conditions of Mild Hypercholesterolemia

“…IFN-␥ upregulates IL-1 and TNF-␣ production, cytokines that are pivotal protein mediators of inflammation 24 and upregulate adhesion molecule expression on vascular endothelial cells. 25,26 Gupta et al, 27 using compound apoE-deficient, IFN-␥ receptor-deficient mice, showed that IFN-␥ can potentiate murine atherosclerosis through both local effects in the arterial wall and systemic effects on plasma lipoproteins. Conversely, Th2-derived IL-4 inhibits proinflammatory cytokine release.…”