1. Interleukin 23 Levels Are Increased in Carotid Atherosclerosis Possible Role for the Interleukin 23/Interleukin 17 Axis
- Author
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Christen P. Dahl, Lars Holger Alteheld, Pål Aukrust, Bente Halvorsen, Karolina Skagen, D. Bundgaard, Azhar Abbas, Kirsten Krohg-Sørensen, Erik A.L. Biessen, David Russell, Vigdis Bjerkeli, Tuva B. Dahl, Sverre Holm, Azita Rashidi, Mona Skjelland, Trine Almås, Ida Gregersen, Annika E. Michelsen, Isabelle Daissormont, Promovendi CD, Pathologie, and RS: CARIM - R3 - Vascular biology
- Subjects
Carotid atherosclerosis ,Carotid Artery Diseases ,Male ,medicine.medical_treatment ,Inflammation ,Interleukin-23 ,Interleukin 23 ,Medicine ,Humans ,RNA, Messenger ,Aged ,Advanced and Specialized Nursing ,business.industry ,Interleukin-17 ,Interleukin ,Receptors, Interleukin ,Middle Aged ,Plaque, Atherosclerotic ,Stroke ,Cytokine ,interleukins ,Gene Expression Regulation ,inflammation ,Immunology ,Leukocytes, Mononuclear ,carotid stenosis ,Female ,Neurology (clinical) ,Interleukin 17 ,medicine.symptom ,atherosclerosis ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
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.
- Published
- 2015