Background—Atherosclerosis is an inflammatory disease in which interferon (IFN)-, 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.

Methods and Results—Circulating IL-17 and IFN- 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-/CXCL10 cytokine axis but not with known Th17 inducers such as IL-1, IL-6, and IL-23. Both IL-17 and IFN- 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- but not IL-17 secretion. Blockade of IFN- signaling increased IL-17 synthesis, whereas neutralization of IL-17 responses decreased IFN- synthesis; production of both cytokines was inhibited by transforming growth factor-1. Approximately 10-fold fewer coronary artery–infiltrating T helper cells were IL-17 producers than IFN- producers, and unexpectedly, IL-17/IFN- 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- to enhance IL-6, CXCL8, and CXCL10 secretion.

Conclusions—Our findings demonstrate that IL-17 is produced concomitantly with IFN- by coronary artery–infiltrating T cells and that these cytokines act synergistically to induce proinflammatory responses in vascular smooth muscle cells.