Monoclonal antibodies targeting IL-1 beta reduce biomarkers of atherosclerosis in vitro and inhibit atherosclerotic plaque formation in Apolipoprotein E-deficient mice

Genetic inactivation of IL-1 signaling enhances atherosclerotic plaque instability and reduces outward vessel remodeling in advanced atherosclerosis in mice

“…IL-1α and IL-1β are found in human atherosclerotic plaques, where they are released primarily by endothelial cells and macrophages (18,19). Genetic inactivation and pharmacological inhibition of IL-1α, IL-1β, and IL-1R1 have been shown to decrease atherosclerotic plaque formation within the aortic root and thoracoabdominal aorta in mice (20)(21)(22)(23)(24)(25), demonstrating a pro-atherogenic role for IL-1 in promoting atherosclerotic lesion formation. However, these studies have focused almost exclusively on the effects of IL-1 on lesion size and the extent of lesion formation, and a comprehensive analysis of the role of IL-1 in regulating features of plaque stability and outward vessel remodeling in advanced atherosclerosis has not been performed.…”

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

“…Stimuli, such as b-FGF, TGF-b and IL-1b and other soluble cytokines as well as oxidized compounds, indeed trigger MMP-9 expression (Chen et al, in press, 2011a,b;Seizer et al, 2010), whereas conditions that reduce secretion of these pro-inflammatory cytokines affects the MMP-9 content as well (Bhaskar et al, 2011;Sigala et al, 2010). Reactions by-products in the inflammatory context further induce the aberrant activation of proMMP-9 (Bonacci et al, 2011).…”

Type 2 Diabetes, Immunity and Cardiovascular Risk: A Complex Relationship

“…A recent study tested in mice the efficacy of a high affinity monoclonal antibody to IL-1 , XOMA 052, showing an inhibition of atherosclerotic plaques formation (Bhaskar et al, 2011). Although clinical trials testing this antibody in T2DM patients failed in demonstrating an improvement in glycemic control, XOMA 052 potentially might reduce cardiovascular risk, since its administration in diabetic patients was associated with a reduction of inflammatory markers and increased levels of high-density lipoprotein.…”