Interleukin-17 and interferon-γ Are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells

Raymond E. Eid, Deepak A. Rao, Jing Zhou, Sheng Fu L. Lo, Hooman Ranjbaran, Amy Gallo, Seth I. Sokol, Steven Pfau, Jordan S. Pober, George Tellides

Research output: Contribution to journalArticlepeer-review

Abstract

Atherosclerosis is an inflammatory disease in which interferon (IFN)-γ, the signature cytokine of Th1 cells, plays a central role. We investigated whether interleukin (IL)-17, the signature cytokine of Th17 cells, is also associated with human coronary atherosclerosis. Circulating IL-17 and IFN-γ were detected in a subset of patients with coronary atherosclerosis and in referent outpatients of similar age without cardiac disease but not in young healthy individuals. IL-17 plasma levels correlated closely with those of the IL-12/IFN-γ/CXCL10 cytokine axis but not with known Th17 inducers such as IL-1β, IL-6, and IL-23. Both IL-17 and IFN-γ were produced at higher levels by T cells within cultured atherosclerotic coronary arteries after polyclonal activation than within nondiseased vessels. Combinations of proinflammatory cytokines induced IFN-γ but not IL-17 secretion. Blockade of IFN-γ signaling increased IL-17 synthesis, whereas neutralization of IL-17 responses decreased IFN-γ synthesis; production of both cytokines was inhibited by transforming growth factor-β1. Approximately 10-fold fewer coronary artery-infiltrating T helper cells were IL-17 producers than IFN-γ producers, and unexpectedly, IL-17/IFN-γ double producers were readily detectable within the artery wall. Although IL-17 did not modulate the growth or survival of cultured vascular smooth muscle cells, IL-17 interacted cooperatively with IFN-γ to enhance IL-6, CXCL8, and CXCL10 secretion. Our findings demonstrate that IL-17 is produced concomitantly with IFN-γ by coronary artery- infiltrating T cells and that these cytokines act synergistically to induce proinflammatory responses in vascular smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)1424-1432
Number of pages9
JournalCirculation
Volume119
Issue number10
DOIs
StatePublished - Mar 17 2009
Externally publishedYes

Keywords

  • Coronary disease
  • Inflammation
  • Interleukins
  • Lymphocytes
  • Muscle
  • Smooth

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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