PLoS ONE (Jan 2013)

Increased systemic and local interleukin 9 levels in patients with carotid and coronary atherosclerosis.

  • Ida Gregersen,
  • Mona Skjelland,
  • Sverre Holm,
  • Kirsten B Holven,
  • Kirsten Krogh-Sørensen,
  • David Russell,
  • Erik T Askevold,
  • Christen P Dahl,
  • Stein Ørn,
  • Lars Gullestad,
  • Tom E Mollnes,
  • Thor Ueland,
  • Pål Aukrust,
  • Bente Halvorsen

DOI
https://doi.org/10.1371/journal.pone.0072769
Journal volume & issue
Vol. 8, no. 8
p. e72769

Abstract

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OBJECTIVE: Atherosclerosis 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. METHODS: Plasma 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. RESULTS: THE 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. CONCLUSION: Our 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.