Interleukin 23 Levels Are Increased in Carotid Atherosclerosis

Stroke is one of the major causes of death and disability worldwide. Approximately 85% of all strokes are ischemic, and 20% to 30% of these are caused by carotid atherosclerosis. Moderateto high-grade carotid artery stenosis can be detected in 1% to 3% of adults, and the incidence increases with age. Along with the degree of stenosis, inflammation and plaque composition are important in predicting the risk of clinical symptoms. The atherosclerotic plaque is composed of infiltrating inflammatory cells (eg, monocytes/macrophages, T cells, and dendritic cells [DCs]), smooth muscle cells, and lipids. Plaques prone to rupture have thin fibrous caps and high-grade inflammation. The balance between proand anti-inflammatory mediators is therefore of major importance for the fate of the plaque and for the occurrence of adverse events. Background and Purpose—Interleukin (IL)-23 is a cytokine in the IL-12 family, mainly produced by antigen-presenting cells with a central role in inflammation. We hypothesize that IL-23 is also important in atherogenesis and investigate this in a population with carotid atherosclerosis. Methods—Plasma levels of IL-23 were measured in patients with carotid artery stenosis and in healthy controls. The mRNA levels of IL-23 and its receptor, IL-23R, were measured in atherosclerotic plaques, nonatherosclerotic vessels, peripheral blood mononuclear cells, and plasmacytoid dendritic cells. Results—Our findings were as follows: (1) patients with carotid atherosclerosis (n=177) had significantly raised plasma levels of IL-23 when compared with healthy controls (n=24) with particularly high levels in those with the most recent symptoms. (2) mRNA levels of IL-23 and IL-23R were markedly increased in carotid plaques (n=68) when compared with nonatherosclerotic vessels (n=8–10). Immunostaining showed colocalization to plaque macrophages. (3) Patients with carotid atherosclerosis had increased mRNA levels of both IL-23 and IL-23R in plasmacytoid dendritic cells, but not in peripheral blood mononuclear cells. (4) IL-23 increased IL-17 release in monocytes and particularly in peripheral blood mononuclear cells from patients with carotid atherosclerosis, but not in cells from healthy controls. (5) IL-23 gave a prominent tumor necrosis factor release in monocytes from patients with carotid atherosclerosis but not in cells from healthy controls. (6) High plasma levels of IL-23 were associated with increased mortality during follow-up. Conclusions—We have shown an association between IL-23 and disease progression in patients with carotid atherosclerosis, potentially involving IL-17-related mechanisms. (Stroke. 2015;46:793-799. DOI: 10.1161/STROKEAHA.114.006516.)