Stage-dependent differential effects of interleukin-1 isoforms on experimental atherosclerosis

Abstract

Aims Targeting interleukin-1 (IL-1) represents a novel therapeutic approach to atherosclerosis. CANTOS demonstrated the benefits of IL-1β neutralization in patients post-myocardial infarction with residual inflammatory risk. Yet, some mouse data have shown a prominent role of IL-1α rather than IL-1β in atherosclerosis, or even a deleterious effect of IL-1 on outward arterial remodelling in atherosclerosis-susceptible mice. To shed light on these disparate results, this study investigated the effect of neutralizing IL-1α or/and IL-1β isoforms starting either early in atherogenesis or later in ApoE–/– mice with established atheroma. Methods and results The neutralization of IL-1α or of both IL-1 isoforms impaired outward remodelling during early atherogenesis as assessed by micro-computed tomographic and histologic assessment. In contrast, the neutralization of IL-1β did not impair outward remodelling either during early atherogenesis or in mice with established lesions. Interleukin-1β inhibition promoted a slant of blood monocytes towards a less inflammatory state during atherogenesis, reduced the size of established atheromata, and increased plasma levels of IL-10 without limiting outward remodelling of brachiocephalic arteries. Conclusion This study established a pivotal role for IL-1α in the remodelling of arteries during early experimental atherogenesis, whereas IL-1β drives inflammation during atherogenesis and the evolution of advanced atheroma in mice.

Cholesterol crystals use complement to increase NLRP3 signaling pathways in coronary and carotid atherosclerosis

“…On the other side, Jiang et al [9] recently found that inhibiting the NLRP3 inflammasome using MCC950 reduced LPS- or ATP-induced IL-1α release in plaque-derived tissue. The exact role of IL-1α in atherogenesis is still not clear, however, it seems to be of importance for metabolic-induced inflammation, as it was recently shown to promote vascular remodelling [35] .…”

Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products

“…In addition, these modified LDLs can cause oxidative stress, inflammation, NLRP3 inflammasome activation, and immune response, thus amplifying the vicious cycle of atherogenic cellular events (Steinberg and Witztum, 2010;Wang et al, 2017h). In addition to modified LDL, interleukin 1 (IL-1) (IL-1a and IL-1b) also drives vascular inflammation, with IL-1a mainly being involved in arterial remodeling during the early phase of atherosclerosis, whereas IL-1b drives inflammation and atheroprogression to advanced state of atherosclerosis (Vromman et al, 2019). The recent CANTOS clinical trial has shown that anti-inflammatory effect with canakinumab (a monoclonal antibody targeting IL-1b) significantly reduces the rate of recurrent cardiovascular events in patients with atherosclerotic diseases without reducing the lipid levels (Ridker et al, 2017).…”

IL‐10 induces MC3T3‐E1 cells differentiation towards osteoblastic fate in murine model

“…Osteoblast is responsible for bone formation, [24][25][26] and MC3T3-E1 cells are precursors of osteoblasts. Since IL-10 regulates arthritis development, 12,13 we speculated that IL-10 is involved in the osteogenic capacity of MC3T3-E1 cells.…”