Role of interleukins in the pathogenesis of coronary heart disease: A literature review

Table 2 Overall summary of therapeutic strategies in coronary heart disease

Interleukins	Summary of therapeutic strategies	Ref.
IL-1	It suggested that IL-1 and associated cytokines could be therapeutic targets for both stable and unstable CAD. Statins' capacity to alter this system in an anti-inflammatory manner emphasizes their potential for immunomodulation. Commonly used medicinal compounds or specific molecules with focused anti-inflammatory effects can target these molecules. Together with newer treatments like TNF-α inhibitors and IL-1 receptor antagonists, the most important anti-inflammatory medications include aspirin, statins, colchicine, IL-1β inhibitors, and IL-6 inhibitors. Because of their pleiotropic and anti-inflammatory properties, aspirin and statins are well-established treatments for atherosclerosis and CAD. Identifying patients with high inflammatory profiles (e.g., elevated IL-1β or hsCRP levels) could help tailor anti-inflammatory interventions. Investigating the roles of IL-1α and IL-1 receptor antagonists in CHD could further refine therapeutic strategies	[18,73]
IL-2	Immune tolerance is induced and immunological homeostasis is maintained by regulatory T cells. Low-dose IL-2 may be able to boost the number of Treg cells, according to recent in vivo research. Human recombinant IL-2, known as aldesleukin, has been utilized therapeutically to treat several autoimmune disorders. For individuals with ischemic heart disease, larger studies are required to verify the safety and assess the effectiveness of low-dose IL-2 as an anti-inflammatory treatment	[21,22]
IL-3	Not determined
IL-4	Not determined
IL-5	The atheroprotective effects of IL-5 in atherosclerosis have been demonstrated to include promoting B-1 cell differentiation to release more T15/EO6 antibodies, which can inhibit macrophage absorption of oxidized low-density lipoprotein and decrease the production of foam cells. Understanding its complex contributions to immune and vascular processes could lead to new insights and therapeutic strategies for reducing CHD risk and improving cardiovascular outcomes	[27]
IL-6	It revealed that although the IL-6 signaling cascade and the anti-inflammatory effect of HMG-CoA reductase were found to influence the risk of CAD. The anti-CAD effect of statins may rely on inflammatory pathways other than the IL-6 signaling cascade. The authors examined the effectiveness and current uncertainties of colchicine, IL-6 receptor antagonists, and IL-1β antibodies in the anti-inflammatory management of coronary atherosclerotic heart disease. Previous studies have indicated that rosuvastatin inhibits c-Jun N-terminal kinase and NF-κB to reduce the inflammatory response. Additionally, adhesion molecules and some cytokines, including IL-8, IL-6, and MCP-1, have been discovered to be decreased by it	[32,73,66]
IL-7	Aspirin was given to healthy control volunteers for seven days at a dose of 160 mg per day, and it decreased the levels of IL-7 in their plasma. It also decreased the release of IL-7 from platelets both spontaneously and in response to SFLLRN stimulation. Blocking IL-7 or its IL-7R may reduce T-cell-mediated inflammation and slow atherosclerosis progression. IL-7R inhibitors are under investigation for autoimmune diseases and could be repurposed for CHD	[39]
IL-8	Patients with CHD who had been taking statins continuously showed a substantial reduction in both transcriptomic and phenotypic IL-8 expression when compared to the H and N group individuals. Consequently, IL-8 need to function as a practical marker and be employed to assess the therapeutic benefits of statins as well as to depict the pathophysiology of CHD therapy. Coronary atherosclerotic plaques are reduced, vascular inflammation is reduced, and bad cholesterol is decreased as a result of atorvastatin and rosuvastatin's therapeutic actions. In this meta-analysis research, intravascular ultrasound imaging showed that both medications may regress the composition of atherosclerotic plaques, raise the coronary artery lumen volume, and dramatically reduce atheroma volume. The rupture that results in vascular occlusion is avoided by the regression and stability of plaque. Blocking IL-8 or its receptors (CXCR1 and CXCR2) may reduce vascular inflammation, immune cell recruitment, and plaque progression. CXCR2 inhibitors are being explored for other inflammatory diseases and may have potential for CHD	[42,71]
IL-9	IL-9 may contribute to the development of CAD and offer an innovative approach to its prevention and management. Blocking IL-9 or its IL-9R may help mitigate vascular inflammation and atherosclerosis progression	[48]
IL-10	Therapeutic approaches that enhance IL-10 activity or mimic its effects hold promise for preventing and treating CHD. IL-10 levels might serve as a biomarker for anti-inflammatory activity and cardiovascular risk stratification	[51-57]

CAD: Coronary artery disease; CHD: Coronary heart disease; CRP: C-reactive protein; CXCR1: C-X-C motif chemokine receptor 1; HMG-CoA: 3-hydroxy-3-methylglutaryl coenzyme A; hsCRP: High-sensitivity C-reactive protein; IL: Interleukin; MCP-1: Monocyte chemoattractant protein-1; NF-kB: Nuclear factor kappa B; TNF-a: Tumor necrosis factor alpha.