Alexander E. Merkler, MD

Grönberg C, Bengtsson E, Fredrikson GN, Nitulescu M, Asciutto G, Persson A, et al. Human Carotid Plaques With High Levels of Interleukin-16 Are Associated With Reduced Risk for Cardiovascular Events. Stroke. 2015

Over the years, we have learned that carotid artery disease is more complex than degree of stenosis. Two patients with identical severities of carotid artery stenosis may have entirely different phenotypes: one patient may develop recurrent strokes or TIAs and the other may remain asymptomatic. Ongoing research evaluating “vulnerable plaque” characteristics such as intraplaque hemorrhage, necrosis, or lipid core volume will hopefully guide physicians to better predict which patients are at risk for stroke and may benefit from a carotid artery intervention.

Interleukin 16 (IL-16) is a cytokine with both pro and anti-inflammatory properties. In the current study, Grönberg et al evaluate whether high levels of IL-16 found in human carotid artery plaques may confer protection against stroke. The authors evaluated 206 asymptomatic and symptomatic carotid artery plaques from human subjects who received carotid endarterectomies. Symptomatic patients had >70% stenosis and asymptomatic patients had >80% stenosis. 

The authors found that IL-16 mRNA expression was significantly higher in plaques from patients with asymptomatic carotid disease as compared to plaques from symptomatic carotid artery disease. In addition, high levels of IL-16 protein in carotid plaques were associated with a decreased incidence of future cerebrovascular events. Furthermore, high levels of IL-16 were associated with markers of plaque stability including elastin and collagen.

Some limitations to consider include 1) the lack of MRI data on radiographical plaque morphology –ie: amount of hemorrhage or calcification and 2) lack of causality – instead of high levels of IL-16 being protective against stroke, perhaps, in patients with symptomatic carotid disease, stroke may lead to decreased levels of IL-16 through post-stroke immunodepression and subsequent plaque destabilization.

Overall, IL-16 seems to be associated with carotid plaque stabilization and a reduced risk of stroke. If these findings are proven true, IL-16 could be a useful target to help reduce complications from large artery atherosclerosis.