Increased Systemic and Local Interleukin 9 Levels in Patients with Carotid and Coronary Atherosclerosis

Abstract

ObjectiveAtherosclerosis is a chronic inflammatory disorder that involves a range of inflammatory mediators. Although interleukin (IL)-9 has been related to inflammation, there are at present no data on its role in atherosclerosis. Here we have examined IL-9 and IL-9 receptor (IL-9R) systemically and locally in patients with coronary and carotid atherosclerosis.MethodsPlasma IL-9 was quantified by enzyme immunoassay and multiplex technology. IL-9 and IL-9R mRNA were quantified by real-time RT-PCR, and their localization within the lesion was assessed by immunohistochemistry.ResultsThe main findings were: (i) Patients with carotid atherosclerosis had significantly raised IL-9 plasma levels compared with healthy controls (n = 28), with no differences between asymptomatic (n = 56) and symptomatic (n = 88) patients. (ii) On admission, patients with acute ST-elevation myocardial infarction (STEMI) (n = 42) had markedly raised IL-9 plasma levels which gradually declined during the first week post-MI. (iii) T cells and monocytes from patients with unstable angina (n = 17) had increased mRNA levels of IL-9 as compared with controls (n = 11). (iv) Carotid plaques (n = 68) showed increased mRNA levels of IL-9 and IL-9R compared to non-atherosclerotic vessels (n = 10). Co-localization to T cells (IL-9 and IL-9R) and macrophages (IL-9) were shown by immunohistochemistry. (v) IL-9 increased IL-17 release in peripheral blood mononuclear cells from patients with unstable angina (n = 5) and healthy controls (n = 5) with a particularly enhancing effect in cells from the patient group.ConclusionOur findings show increased IL-9 levels in different atherosclerotic disorders both systemically and within the lesion, suggesting a role for the IL-9/IL-9R axis in the atherosclerotic process, potentially involving IL-17 mediated mechanisms. However, the functional consequences of these findings should be further investigated.

Novel Biomarker MicroRNAs for Subtyping of Acute Coronary Syndrome: A Bioinformatics Approach

“…As shown in Table S3, 28 of the 35 AMI pathways were reported to be involved with AMI and 10 of them are in the group of immune responses, such as CD40 signaling [45, 46]. Many interleukin (IL) factors were also reported in immune response pathways related to AMI such as IL-9 [47], IL-10 [48], IL-17 [49], IL-18 [50], and IL-33 [51]. In the development group, there were five pathways related to AMI, including WNT [52], G-CSF [53], SDF-1 [54], NF-kB [55], PEDF [56], and VEGF [57].…”

IL-17A Influences Essential Functions of the Monocyte/Macrophage Lineage and Is Involved in Advanced Murine and Human Atherosclerosis

“…IL-17A tissue release is more abundant in patients with ischemic symptoms and complicated lesions, but interestingly independent of the standard coronary artery disease medication (13). IL-9, known to facilitate Th17 cell expansion and to stimulate production of IL-17, is increased systemically and locally in patients with carotid and coronary atherosclerosis and increased IL-17 release in PBMCs from patients with unstable angina (28). Focusing on the cellular origin, predominantly macrophages, but also T cells, mast cells, and B cells, express IL-17A (12,13).…”

Cytokines of the Immune System

“…56 Interestingly, 5% of mice transgenic for IL9 get thymic lymphomas. Deregulated production of IL-9 may have a role in oncogenesis of T lineage tumors.…”