The role and transformative potential of IL-19 in atherosclerosis

Wujun Chen; Jiyao Xing; Xinlin Liu; Shuai Wang; Dongming Xing

doi:10.1016/j.cytogfr.2021.09.001

The role and transformative potential of IL-19 in atherosclerosis

Cytokine Growth Factor Rev. 2021 Dec:62:70-82. doi: 10.1016/j.cytogfr.2021.09.001. Epub 2021 Sep 21.

Authors

Wujun Chen¹, Jiyao Xing¹, Xinlin Liu¹, Shuai Wang², Dongming Xing³

Affiliations

¹ Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong 266071, China.
² School of Medical Imaging, Radiotherapy Department, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261053, China. Electronic address: sdwftcmws@163.com.
³ Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong 266071, China; School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: xdm_tsinghua@163.com.

PMID: 34600839
DOI: 10.1016/j.cytogfr.2021.09.001

Abstract

Atherosclerotic cardiovascular disease is the leading cause of death worldwide. Traditionally, IL-19 was thought to be expressed in only immune cells, but studies revealed that IL-19 is also expressed in multiple atherosclerotic plaque cell types, but not normal arteries, in humans and mice. IL-19 reduces the development of atherosclerosis via multiple mechanisms, including balancing cholesterol metabolism; enhancing Th2 immune cell polarization; reducing the inflammatory response; and reducing the proliferation, migration and chemotaxis of vascular smooth muscle cells (VSMCs). Clinical and/or animal studies have primarily aimed to achieve regression and/or stabilization of atherosclerotic plaques, with regression in particular indicating a very good drug response. Most antiatherosclerotic drugs in current clinical use, including atorvastatin and alirocumab, target hyperlipidemia. Several other drugs have also been investigated in clinical trials as anti-inflammatory agents; the development of some of these agents has been terminated (canakinumab, darapladib, varespladib, losmapimod, atreleuton, setileuton, PF-04191834, veliﬂapon, and methotrexate), but others remain in development (ziltivekimab, tocilizumab, Somalix, IFM-2427, anakinra, mesenchymal stem cells (MSCs), colchicine, everolimus, allopurinol, and montelukast). Most of the tested drugs have shown a limited ability to reverse atherosclerosis in animal studies. Interestingly, recombinant IL-19 (rIL-19) was shown to reduce atherosclerosis development in a time- and dose-dependent manner. A low dose of rIL-19 (1 ng/g/day) reduced aortic arch and root plaque areas by 70.1% and 32.1%, respectively, in LDLR^-/- mice. At 10 ng/g/day, rIL-19 completely eliminated atherosclerotic plaques. There were no sex differences in the effects of rIL-19 on atherosclerotic mice. Thus, low-dose rIL-19 is an effective antiatherosclerotic agent, in addition to its efficacy in intimal hyperplasia, spinal cord injury, stroke, and multiple sclerosis. We propose that IL-19 is a promising biomarker and target for the diagnosis and treatment of atherosclerosis. This review considers the role and mechanism of action of IL-19 in atherosclerosis and discusses whether IL-19 is a potential therapeutic target for this condition.

Keywords: Analysis of preclinical studies; Atherosclerosis; Drug; IL-19; Inflammation.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antibodies, Monoclonal, Humanized
Atherosclerosis* / drug therapy
Disease Models, Animal
Mice
Plaque, Atherosclerotic* / drug therapy
Signal Transduction

Substances

Antibodies, Monoclonal, Humanized
ziltivekimab