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

Table 1 Origin/source, functions, and pathophysiological aspects of interleukins in coronary heart disease

Interleukins	Origin/source	Functions	Pathophysiological aspects	Ref.
IL-1	Monocytes, macrophages, lymphocytes, neutrophils, fibroblasts	Lymphocyte activation, fever, regulates sleep, pro-inflammatory cytokine, maturation and proliferation	It has been shown that chronic administration of IL-1β to the myocardial and coronary arteries causes cardiac dysfunction and coronary arteriosclerosis. Pericardial IL-1β concentrations could indicate the degree of ischemic heart disease, and high levels of IL-1β in pericardial fluid might also directly encourage the development of coronary atherosclerosis. It was shown that the adventitial vessel walls of atherosclerotic coronary arteries had higher levels of IL-1β protein than coronary arteries from non-ischemic cardiomyopathic hearts. This rise correlated directly with the degree of coronary atherosclerosis	[13,14]
IL-2	Th1 cells	Stimulates growth of T cells	Not determined
IL-3	Th cells and mast cells	Stimulates bone marrow growth	Patients with CAD, especially those who are symptomatic and receiving percutaneous coronary intervention, have higher levels of IL-3, a key regulator of chronic inflammation. Moreover, a correlation between symptomatic restenosis and elevated IL-3 concentrations was discovered	[23]
IL-4	Th2 cells, basophils, NKT cells	B-cell growth factor, role in tissue adhesion and inflammation	Serum IL-4 levels are reliable indicators of CAD	[19]
IL-5	T cells	Activated T cells, Differentiation and function of myeloid cells	In the coronary plaque of CAD patients, IL-5 was substantially lower than in the group of deceased donors. The coronary artery plaque’s macrophages were the primary source of IL-5. Stable angina pectoris, unstable angina pectoris, and acute myocardial infarction were the sequences from high to low plasma IL-5 levels in the CAD groups, which were considerably lower than those in the non-CAD group. The results of binary linear regression analysis indicated an independent correlation between IL-5 and the incidence of CAD. Th1 and Th17 levels and the mRNA expression of their distinctive cytokines were reduced in CD4+Th cells treated with oxidized low-density lipoprotein after being treated with recombinant mouse IL-5. Near the IL-5 locus, genetic polymorphisms were shown to be strongly linked to coronary artery disease	[25,29]
IL-6	Monocytes, macrophages,	Activated T cells, contributes to host defense through the stimulation of acute phase responses, hematopoiesis	IL-6 helps serve as a reliable biomarker for the degree of CAD as determined by the Gensini score and it is a key factor in the development of atherosclerosis. IL-6 may be a useful marker for assessing the degree of necrosis	[31]
IL-7	Monocytes, macrophages, epithelial cells	T-cell development, survival and homeostasis of mature T cells, B cells and T-cell proliferation	One important factor contributing to the elevated IL-7 levels in angina patients seems to be increased release from activated platelets. Based on interactions between platelets, monocytes, and chemokines, the data point to a role for IL-7-driven inflammation in atherogenesis and the enhancement of clinical instability in CAD	[39]
IL-8	Monocytes and fibroblasts	Angiogenesis, induces chemotaxis, stimulates phagocytosis, neutrophil chemotaxis, superoxide release and granule release	The expression of IL-8 mRNA or plasma IL-8 showed a strong negative connection with the development of CHD. IL-8 plays a part in the progression of CAD occurrences	[42,44]
IL-9	Eosinophils, mast cells	Chemokine, Mast and T-cell growth factor and enhances T-cell survival, mast cell activation and synergy with erythropoietin	IL-9 may interact with established CAD risk factors to cause CAD	[48]
IL-10	Macrophages, T cells, B cells, dendritic cells	Immune suppressed	IL-10 indicates a proinflammatory state in acute coronary syndrome patients. As a result, IL-10 is a biomarker as useful as other systemic inflammation markers for predicting the risk of future cardiovascular events	[53]

CAD: Coronary artery disease; CHD: Coronary heart disease; IL: Interleukin; NKT: Natural killer T; Th1: Type 1 T helper cell.