Interleukin 23 levels are increased in carotid atherosclerosis: possible role for the interleukin 23/interleukin 17 axis

doi:10.1161/STROKEAHA.114.006516

. 2015 Mar;46(3):793-9.

doi: 10.1161/STROKEAHA.114.006516. Epub 2015 Feb 3.

Interleukin 23 levels are increased in carotid atherosclerosis: possible role for the interleukin 23/interleukin 17 axis

Azhar Abbas¹, Ida Gregersen¹, Sverre Holm¹, Isabelle Daissormont¹, Vigdis Bjerkeli¹, Kirsten Krohg-Sørensen¹, Karolina R Skagen¹, Tuva B Dahl¹, David Russell¹, Trine Almås¹, Dorte Bundgaard¹, Lars Holger Alteheld¹, Azita Rashidi¹, Christen P Dahl¹, Annika E Michelsen¹, Erik A Biessen¹, Pål Aukrust¹, Bente Halvorsen², Mona Skjelland¹

Affiliations

¹ From the Research Institute of Internal Medicine (A.A., I.G., S.H., V.B., T.B.D., A.R., C.P.D., A.E.M., P.A., B.H.), Department of Neurology (A.A., K.R.S., D.R., M.S.), Department of Thoracic and Cardiovascular Surgery (K.K.-S.), Department of Cardiology (C.P.D.), and Section of Clinical Immunology and Infectious Diseases (P.A.), Oslo University Hospital Rikshospitalet Oslo, Norway; Department of Neurology, Oslo University Hospital, Ullevål, Norway (L.H.A.); Institute of Clinical Medicine (A.A., I.G., V.B., K.K.-S., T.B.D., D.R., A.E.M., P.A., B.H.), K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research (C.P.D.), K.G. Jebsen Inflammation Research Centre (P.A., B.H.), University of Oslo, Oslo, Norway; Department of Neurology (T.A.), Department of Thoracic and Cardiovascular Surgery (D.B.), Østfold Hospital Trust, Fredrikstad, Norway; and Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands (I.D., E.A.B.).
² From the Research Institute of Internal Medicine (A.A., I.G., S.H., V.B., T.B.D., A.R., C.P.D., A.E.M., P.A., B.H.), Department of Neurology (A.A., K.R.S., D.R., M.S.), Department of Thoracic and Cardiovascular Surgery (K.K.-S.), Department of Cardiology (C.P.D.), and Section of Clinical Immunology and Infectious Diseases (P.A.), Oslo University Hospital Rikshospitalet Oslo, Norway; Department of Neurology, Oslo University Hospital, Ullevål, Norway (L.H.A.); Institute of Clinical Medicine (A.A., I.G., V.B., K.K.-S., T.B.D., D.R., A.E.M., P.A., B.H.), K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research (C.P.D.), K.G. Jebsen Inflammation Research Centre (P.A., B.H.), University of Oslo, Oslo, Norway; Department of Neurology (T.A.), Department of Thoracic and Cardiovascular Surgery (D.B.), Østfold Hospital Trust, Fredrikstad, Norway; and Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands (I.D., E.A.B.). bente.halvorsen@rr-research.no.

PMID: 25649806
DOI: 10.1161/STROKEAHA.114.006516

Interleukin 23 levels are increased in carotid atherosclerosis: possible role for the interleukin 23/interleukin 17 axis

Azhar Abbas et al. Stroke. 2015 Mar.

. 2015 Mar;46(3):793-9.

doi: 10.1161/STROKEAHA.114.006516. Epub 2015 Feb 3.

Authors

Affiliations

¹ From the Research Institute of Internal Medicine (A.A., I.G., S.H., V.B., T.B.D., A.R., C.P.D., A.E.M., P.A., B.H.), Department of Neurology (A.A., K.R.S., D.R., M.S.), Department of Thoracic and Cardiovascular Surgery (K.K.-S.), Department of Cardiology (C.P.D.), and Section of Clinical Immunology and Infectious Diseases (P.A.), Oslo University Hospital Rikshospitalet Oslo, Norway; Department of Neurology, Oslo University Hospital, Ullevål, Norway (L.H.A.); Institute of Clinical Medicine (A.A., I.G., V.B., K.K.-S., T.B.D., D.R., A.E.M., P.A., B.H.), K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research (C.P.D.), K.G. Jebsen Inflammation Research Centre (P.A., B.H.), University of Oslo, Oslo, Norway; Department of Neurology (T.A.), Department of Thoracic and Cardiovascular Surgery (D.B.), Østfold Hospital Trust, Fredrikstad, Norway; and Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands (I.D., E.A.B.).
² From the Research Institute of Internal Medicine (A.A., I.G., S.H., V.B., T.B.D., A.R., C.P.D., A.E.M., P.A., B.H.), Department of Neurology (A.A., K.R.S., D.R., M.S.), Department of Thoracic and Cardiovascular Surgery (K.K.-S.), Department of Cardiology (C.P.D.), and Section of Clinical Immunology and Infectious Diseases (P.A.), Oslo University Hospital Rikshospitalet Oslo, Norway; Department of Neurology, Oslo University Hospital, Ullevål, Norway (L.H.A.); Institute of Clinical Medicine (A.A., I.G., V.B., K.K.-S., T.B.D., D.R., A.E.M., P.A., B.H.), K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research (C.P.D.), K.G. Jebsen Inflammation Research Centre (P.A., B.H.), University of Oslo, Oslo, Norway; Department of Neurology (T.A.), Department of Thoracic and Cardiovascular Surgery (D.B.), Østfold Hospital Trust, Fredrikstad, Norway; and Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands (I.D., E.A.B.). bente.halvorsen@rr-research.no.

PMID: 25649806
DOI: 10.1161/STROKEAHA.114.006516

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.

Keywords: atherosclerosis; carotid stenosis; inflammation; interleukins.

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Interleukin 23 levels are increased in carotid atherosclerosis: possible role for the interleukin 23/interleukin 17 axis

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Interleukin 23 levels are increased in carotid atherosclerosis: possible role for the interleukin 23/interleukin 17 axis

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