Interleukin 23 Levels Are Increased in Carotid Atherosclerosis

Azhar Abbas, Ida Gregersen, Sverre Holm, Isabelle Daissormont, Vigdis Bjerkeli, Kirsten Krohg-Sørensen, Karolina R. Skagen, Tuva B. Dahl, David Russell, Trine Almås, Dorte Bundgaard, Lars Holger Alteheld (+7 others)
2015 Stroke  
793 S troke 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. Moderate-to high-grade carotid artery stenosis can be detected in 1% to 3% of adults, and the incidence increases with age. 1-3 Along with the degree of stenosis, inflammation and plaque composition are important in predicting the risk of clinical symptoms. 4 The atherosclerotic plaque is composed of infiltrating
more » ... nflammatory 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 pro-and anti-inflammatory mediators is therefore of major importance for the fate of the plaque and for the occurrence of adverse events. 5, 6 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 pmid:25649806 fatcat:hd44tzdnvzgidnzjqa7ot63p2u