Human Carotid Plaques With High Levels of Interleukin-16 Are Associated With Reduced Risk for Cardiovascular Events

Abstract

Interleukin 16 (IL-16; previously known as lymphocyte chemoattractant factor) is a chemokine expressed by a variety of different cells such as CD8+ T cells, macrophages, and endothelial cells. 8,9 The IL-16 protein is produced in a pro-IL-16 form, which is later cleaved by caspase-3.10,11 CD4+ T cells have been found in large numbers in the intima, at the site of inflammation and plaque formation. 12 It is known that IL-16 acts as a chemoattractant on CD4+ T cells and is thought to inhibit the T-cell receptor, making the cells incapable of proliferation after antigen stimulation.13 IL-16 is a pleiotropic cytokine with proinflammatory, Th1-promoting Background and Purpose-Interleukin-16 (IL-16) functions as a regulator of T-cell growth and acts as an inducer of cell migration. The aim of this study was to determine whether IL-16 measured in human carotid plaques was associated with symptoms (eg, stroke, transient ischemic attack, or amaurosis fugax), markers of plaque stability, and postoperative cardiovascular events. Methods-Plaques obtained from patients who had ≥1 cerebrovascular ischemic events within 1 month before endarterectomy (n=111) were compared with plaques from patients without symptoms (n=95). Neutral lipids, smooth muscle cell, and macrophage contents were evaluated histologically, and collagen, elastin, and caspase-3 activity were measured biochemically. IL-16, matrix metalloproteinases, and tissue inhibitors of metalloproteinases were measured in plaque homogenates using a multiplex immunoassay. IL-16, CD3, CD4, and FoxP3 mRNA expressions in carotid plaques were analyzed with quantitative real-time polymerase chain reaction. Results-Carotid plaques from asymptomatic patients had higher levels of IL-16 mRNA. High plaque IL-16 protein levels (above median) were associated with reduced incidence of postoperative cardiovascular events during a mean follow-up of 21 months (hazard ratio, 0.47; 95% confidence interval, 0.

Evaluation of Polymorphisms in IL8 and IL16 Genes in Patients with Acute Coronary Syndrome

“…In addition, among the blood donors, the G (TG + GG) allele presented higher IL-16 values (p = 0.01). These results corroborate the data obtained by Gronberg et al, 11,43 where the presence of IL-16 on the carotid plaque is associated with a decreased risk of cardiovascular events in studies performed with a Swedish population. This is due to the stabilization of the atherosclerotic plaques, avoiding the ACS disease.…”

The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins

“…IL-20 is involved in epidermal hyperplasia and inhibits keratinocyte differentiation 59 , but is also expressed in atherosclerotic plaques, and was shown to promote atherosclerosis in a mouse model 60 . IL-16, a chemo-attractant for CD4 + T-helper cells and myeloid cells, is also expressed in atherosclerotic plaques, but may have a plaque-stabilizing effect 61 , 62 . These factors, together with an environment of chronic/Th1-triggered inflammation 4 , 63 , with various degrees of Th17 activation 26 , 64 , 65 , suggest a potentially pro-atherogenic milieu in the blood of both psoriasis and AD patients that may directly impact endothelial cells 66 .…”

Association of functional IL16 polymorphisms with cancer and cardiovascular disease: a meta-analysis

“…Other studies also demonstrated increases in tissue expression and serum concentrations of IL-16 in malignant ovarian tumors [ 26 ] and cutaneous T-cell lymphoma [ 20 , 27 ]. In cardiovascular diseases, high IL-16 serum concentrations were associated with asymptomatic carotid plaques and reduced numbers of cardiovascular events after surgery, suggesting a protective profile in atherosclerosis and the risk of cardiovascular events [ 28 – 30 ]. However, increased levels of this cytokine were also associated with cardiac fibrosis and myocardial stiffening [ 31 ], production of proinflammatory cytokines such as IL-1β and IL-6 [ 32 ], as well as the risk for acute myocardial infarction [ 33 ], being a potential target for CVD treatments [ 34 ].…”