Aim: Interleukin 27 is a member of the IL-12 family of cytokines and is secreted as a heterodimer consisting of Epstein-Barr-induced gene 3 product (EBI3) and p28. The IL-27 receptor is also a heterodimer composed of IL-27Rα and gp130, in which both units are required for signal transduction. IL-27 has both pro- and anti-inflammatory properties and is involved in several different inflammatory diseases. There are only few reports on IL-27 in atherosclerotic disease and the regulation of IL-27 in atherosclerosis is not fully understood. In this study we examine IL-27 levels in carotid atherosclerotic disease as well as effects of this cytokine on a relevant cell line.
Methods: Plasma levels of IL-27 were measured by ELISA in patients with carotid stenosis (n=135) and in healthy controls (n=20). Expression of IL-27 and IL-27R were analyzed by qPCR and immunohistochemistry in plaques from the same patient group. TNF-α –activated THP-1 monocytes were used to study relevant effects of IL-27 in vitro.
Results: Plasma levels of IL-27 were significantly elevated in patients with carotid atherosclerotic disease compared to healthy controls. IL-27 and IL-27R mRNA expression were significantly elevated in plaques when compared to control vessels. Protein expression in the carotid plaque was confirmed by immunohistochemistry. In vitro, IL-27 (100 ng/ml) induced production of pro-inflammatory cytokines from TNF-α activated THP-1 cells.
Conclusions: We demonstrate increased levels of circulating IL-27 and expression of IL-27 and IL-27R in plaque from patients with carotid atherosclerosis. Our in vitro findings may suggest a pro-inflammatory role for IL-27, which can possibly be linked to atherosclerotic disease development.