Question

What role does IL-B play in atherosclerosis. Include at least two references

IL-1B. Interleukin 1 beta.

Answer 1

Atherosclerosis contributes to the development of many cardiovascular diseases, which remain the leading cause of death in developed countries. Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries. It is caused by dyslipidemia and mediated by both innate and adaptive immune responses. Inflammation is a key factor at all stages of atherosclerosis progression.....One inflammatory mediator has come to the fore as a therapeutic target in cardiovascular disease. The experimental and clinical evidence reviewed here support interleukin-1 beta (IL-1β) as both a local vascular and systemic contributor in this regard. Intrinsic vascular wall cells and lesional leukocytes alike can produce this cytokine. Local stimuli in the plaque favor the generation of active IL-1β through the action of a molecular assembly known as the inflammasome. Clinically applicable interventions that interfere with IL-1 action can improve cardiovascular outcomes, ushering in a new era of anti-inflammatory therapies for atherosclerosis. The translational path described here illustrates how advances in basic vascular biology may transform therapy. Biomarker-directed application of anti-inflammatory interventions promises to help us achieve a more precise and personalized allocation of therapy for our cardiovascular patients.

Two receptors bind the principal members of the IL-1 family. IL-1 receptor I transduces IL-1β signaling ...In contrast, the IL-1 receptor II (IL-1RII) binds the ligands but does not signal, as it lacks a cytoplasmic domain. IL-1RII thus functions as a “decoy,” providing yet another level of negative regulation of IL-1 signaling. IL-1 can induce its own gene expression in many cell types, including those implicated in atherogenesis....In the case of IL-1α or IL-1β inducing themselves or each other, a positive feedback loop pertains....IL-1α and IL-1β can also increase the expression of IL-1ra, enabling negative feedback inhibition—a mechanism that prevents untrammeled IL-1 signaling......

Inflammatory pathways drive atherogenesis and link traditional risk factors to atherosclerosis and its complications. Interleukin-1 beta (IL-1β) has emerged as an actionable mediator in prevention of recurrent cardiovascular events. Intrinsic vascular wall cells and lesional leukocytes alike can produce this pro-inflammatory cytokine. Local stimuli in the plaque boost the generation of active IL-1β through the action of a molecular assembly known as the inflammasome. Therapies that interfere with IL-1 action can improve cardiovascular outcomes, ushering in a new era of anti-inflammatory therapies for atherosclerosis. Biomarker-directed application of anti-inflammatory interventions promise to personalize allocation of therapy for our cardiovascular patients.

IL-1β is a potent pro-inflammatory cytokine produced by cells of the innate immune system. It is produced without a signal sequence and does not follow the conventional route of protein secretion, but rather employs one or more non-conventional pathways of secretion. In an attempt to consolidate the many disparate observations on IL-1β release from the literature, and to provide a rationale for their existence, all mechanisms are part of one continuum of secretion, or a spectrum , where the routes of secretion employed are dictated by the strength of the inflammatory stimulus and thus the levels of IL-1β required extra cellularly to mount an effective inflammatory response....the non-conventional secretion of IL-1β as a continuum dependent upon the extracellular requirement of IL-1β, it has been possible to rationalise a context in which all mechanisms contribute to the secretion of IL-1β..